New GEO Series

GSE329361 DNA repair drives cisplatin-induced neuronal death

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Jeroen van den Berg ; Willian Nathan ; Andre Nussenzweig
Series Type : Other
Organism : Homo sapiens

Cisplatin and similar alkylating chemotherapy agents are the cornerstone treatments for many types of cancers. While effective, these drugs induce long-term side-effects in post-mitotic tissues including the nervous system. There are no known effective pharmacological interventions for chemotherapy-induced neurotoxicities, in part due to our limited understanding of how neurons and other non-dividing cells respond to DNA damage. Here, we show that nucleotide excision repair (NER) is responsible for cisplatin adduct removal in human neurons. However, contrary to its protective role in dividing cells, NER drives neuronal cell death in response to cisplatin. Through DNA repair synthesis, NER exhausts low levels of deoxynucleoside triphosphate (dNTP) pools found in post-mitotic neurons. dNTP pools are first consumed to resolve transcription blocking lesions through transcription-coupled NER. When dNTPs become exhausted, toxic double-strand breaks accumulate across the genome primarily because of incomplete global-genome NER. Supplementation with deoxynucleosides (dN) or genetic upregulation of dNTP production protects neurons from cisplatin-induced cell death. These results identify low levels of endogenous dNTP pools as a vulnerability of post-mitotic cells to DNA damage and suggest nucleoside supplementation as a strategy to protect patients from chemotherapy-induced neurotoxicity.

GSE329327 Queuosine promotes wecB-dependent phage resistance and biofilm formation in marine bacterium Shewanella glacialimarina

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Pavlina Gregorova ; Minna-Maria K Heinonen ; Nina Sipari ; Peter Sarin
Series Type : Expression profiling by high throughput sequencing
Organism : Shewanella glacialimarina

Transfer RNA (tRNA) modifications critically fine-tune translational accuracy and efficiency, influencing bacterial adaptation to environmental challenges. Among these, the queuosine (Q) modification has recently emerged as a regulator of biofilm formation, yet its role during phage infection remains unknown. Here, we investigate how Q modification links host translational control to phage infection. We show that phage infection activates the Q biosynthetic pathway, leading to elevated Q levels and enhanced translation of NAT-biased genes. This shift drives two interconnected outcomes, namely increased biofilm formation and enhanced mutagenesis mediated by translesion synthesis polymerases. We further identify conserved, slippage-prone regions within surface-related genes that act as hotspots for adaptive variation. Together, our findings uncover a novel mechanistic link between tRNA modification and phage-driven bacterial diversification.

GSE329316 Transcriptome sequencing of cavernous fibroblasts cultured on substrates with different stiffness.

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Biao Liu ; Yuzhuo Chen
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Fibrotic diseases involve increased mechanical stress due to extracellular matrix deposition, significantly altering cellular metabolism. However, a systematic understanding of how mechanical force regulates lipid metabolism across different molecular layers remains limited. We employed an integrated multi-omics approach, including transcriptomics, Ribo-seq, proteomics, and lipidomics, to comprehensively assess the effects of mechanical stretch on lipid metabolism in human cavernous fibroblasts. Our analysis revealed that while mechanical force elicits complex multi-layered responses, post-translational regulation predominantly drives this lipid metabolic reprogramming. Lipidomics identified a significant reduction in fatty acids and an upregulation of ganglioside. Key genes central to this mechanosensitive metabolic shift were pinpointed. This study demonstrates that mechanical force hierarchically reprograms lipid metabolism. The shift from fatty acids to ganglioside underscores a key metabolic adaptation in fibroblasts. Targeting the identified critical genes may offer a promising therapeutic strategy for fibrosis-related diseases.

GSE329307 Ribo-seq of cavernous fibroblasts cultured on substrates with different stiffness.

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Biao Liu ; Yuzhuo Chen
Series Type : Other
Organism : Homo sapiens

GSE329274 Phosphorylated DEK sustains leukemia stem cells by enabling PBX3-driven transcriptional reprogramming [CUT&Tag 2]

Tue, 28 Apr 2026 00:00:00 -0400

Contributor : Zhe Chen
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens

Leukemia stem cells (LSCs) drive acute myeloid leukemia (AML) initiation, relapse, and chemoresistance, yet the core post-translational events governing LSC formation and maintenance remain elusive. Here, through phosphoproteomic profiling of normal hematopoietic stem and progenitor cells (HSPCs) versus LSC-enriched population, we identify DEK phosphorylation as a critical modification during leukemogenesis. Functional studies in MLL-AF9- and HOXA9/MEIS1-driven AML mouse models, as well as patient-derived xenografts (PDXs), demonstrate that DEK deficiency impairs LSC maintenance and AML development. Moreover, DEK deletion enhances LSC chemosensitivity to the standard-of-care combination of azacitidine and venetoclax (Aza/Ven), whereas DEK overexpression confers robust chemoresistance. Mechanistically, DEK recruits the transcription factor GABPA to drive overexpression of transcriptional cofactor PBX3, a key oncogenic driver in AML, thereby sustaining a leukemogenic transcriptional program. This DEK-GABPA interaction strictly depends on DEK phosphorylation at Ser301/303/306/307 (the 4S site), which stabilizes the conformation of the DEK-GABPA complex. We demonstrate CK2 as the upstream kinase that directly phosphorylates DEK-4S site. Importantly, inhibition of DEK phosphorylation through 4S site mutations or treatment with a clinical-stage CK2 inhibitor CX-4945 selectively depletes LSCs while sparing normal HSPCs. Furthermore, combining CX-4945 with venetoclax promotes LSC apoptosis and suppresses the PBX3-mediated leukemogenic transcriptional program, exhibiting synergistic anti-AML effects both in vitro and in vivo. Collectively, our findings uncover a previously unrecognized phosphorylation event (DEK-4S phosphorylation) that sustains LSCs and establish the CK2-DEK axis as a promising LSC-specific therapeutic strategy in AML.

GSE329270 Phosphorylated DEK sustains leukemia stem cells by enabling PBX3-driven transcriptional reprogramming [ATAC-seq 2]

Tue, 28 Apr 2026 00:00:00 -0400

Contributor : Zhe Chen
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens

GSE329105 Vitrification of Culter alburnus Embryos by Laser-Assisted Warming with Gold Nanorods

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Xinqing Cai ; Yuting Luo ; Hongkuan Song ; Jiamin Wang ; Yipeng Ren ; Bingshe Han ; Junfang Zhang
Series Type : Expression profiling by high throughput sequencing
Organism : Culter alburnus

Cryopreservation of fish embryos is highly challenging, and to date, successful reports of fish embryo cryopreservation remain scarce. In this study, we optimized the vitrification solution and employed gold nanorods (GNRs) in a laser-assisted warming process to improve the hatching rate of Culter alburnus embryos after cryopreservation. With V11 vitrification solution (15% DMSO, 10% EG, 15% PG, and 1 mM MT) and a laser-assisted warming condition (25 μg/mL GNRs with continuous 15 W laser irradiation), we achieved rapid and homogeneous warming, and the mean hatching rate of cryopreserved embryos reached 18.83%. RNA-seq revealed that above cryopreservation procedure led to significant transcriptional changes in calcium signaling pathways and apoptosis-related genes, which may facilitate further optimization of vitrification solution. This study provides a basis for further improving the efficiency of embryo cryopreservation in Culter alburnus and other fish species.

GSE329043 Disrupted glial-mediated synaptic refinement in Fragile X syndrome

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Lindsey Starr ; Melissa Lee ; Amy Vo ; Maia Weisenhaus ; Lucas Cheadle ; Archana Yadav ; Fahad Paryani ; Michelle Shirasu-Hiza ; Vilas Menon ; Carol Mason
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism, results from the loss of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP is a translational regulator and is highly expressed in glial cells, where its role in neural circuit development remains poorly defined. Here, it was observed that Fmr1 knockout mice exhibit reduced synapse size and accelerated eye-specific segregation. To examine which cell-types participate in this process, a multi-omic framework was applied to FXS model mice at postnatal day 7, a critical window for synaptic remodeling in the retinogeniculate pathway, an established model system utilized to study synaptic pruning. Single-cell transcriptomics revealed coordinated alterations in microglia, astrocytes, and neurons in genes linked to synaptic pruning. Computational modeling further demonstrated enhanced astrocyte-to-microglia signaling, particularly through Ephrin A (EphA)- and semaphorin-mediated pathways, while lipidomic profiling revealed reductions in EphA-associated lipid species required for lipid raft stability and receptor localization. Consistent with these observations, a glial engulfment assay indicated that FXS microglia and astroglia over-engulf synaptic material in the lateral geniculate nucleus, supporting the transcriptomic profile. Together, these findings identify impaired glial-driven synaptic refinement as an early mechanistic feature of FXS pathogenesis, highlighting the genes involved in this process as potential therapeutic targets during circuit development.

GSE328992 Beyond ACE2: DPP4 Engagement Redefines SARS-CoV-2 Receptor Tropism

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Yu Zhang ; Jing Li ; Yumeng Li ; Zhuangzhuang Shi ; Yunkai Zhu ; Tiecheng Wang ; Xiaoyang Zhou ; Lu Dai ; Shanshan Yang ; Ruixuan Wang ; Peng Xie ; Mengyao Yu ; Li Gao ; Jiaxin Hu ; Tao Jiang ; Lin Li ; Weiyang Sun ; Yuzhang Wu ; Liqun Fang ; Yuwei Gao ; Jintao Li
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The continued evolution of SARS-CoV-2 has produced variants with enhanced transmissibility despite reduced binding affinity to the canonical entry receptor ACE2, suggesting the involvement of additional host factors. Here, we integrate large-scale sequence analysis, structure-informed machine learning, biochemical assays, cell-based entry models, and in vivo infection studies to examine receptor usage diversification in recent SARS-CoV-2 variants. We find that multiple post-Omicron lineages, including XBB-derived variants, exhibit increased functional engagement of dipeptidyl peptidase 4 (DPP4), accompanied by reduced reliance on ACE2-mediated entry in defined experimental contexts. In human DPP4 knock-in mice, representative XBB variants display enhanced replication with limited pulmonary pathology. Together, these findings support a model in which SARS-CoV-2 evolution is characterized by diversification of receptor engagement strategies, highlighting DPP4 as a functionally relevant entry factor that may contribute to viral fitness under immune pressure.

GSE328966 Resilience to Diabetic Retinopathy (RDR) is Associated with a Pre-Retinopathy Transcriptional Program Induced by Diabetes

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Janani Rajasekar ; Maria Paula Zappia ; Maximilian A McCann ; Maxim V Frolov ; Andrius Kazlauskas
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The purpose of this project was to define gene expression changes associated with the acquisition and loss of resilience to diabetic retinopathy (RDR) in individual retinal cell types. Diabetes mellitus (DM) was induced with streptozotocin in male C57Bl6J mice. Single-cell RNA sequencing was performed on retinas from mice that experienced DM for 5 or 15 days, along with retinas from age-matched, non-DM mice. The resulting data sets were analyzed to identify DM-associated differentially expressed genes and pathway enrichments after each duration of DM. We observed that acquisition of RDR, shown to occur after 5 days of DM, was linked to altered expression of genes in a subset of retinal cells, mainly Müller cells. Pathway analysis indicated enhancement of numerous modes of protection, including reinforced neurovascular and structural homeostasis through phagocytosis, integrin signaling, and interferon-mediated defense. After 15 days of DM, when RDR is waning, this pro-protection surge in gene expression subsided. We conclude that a duration of DM that is too short to cause diabetic retinopathy (DR) nonetheless evoked a profound change in the gene expression profile within a subset of retinal cell types. The nature and timing of this molecular shift indicated that it was not the preamble to DM-related damage that eventually develops. Rather, DM engaged numerous defense programs within Müller cells. These observations provide a molecular foundation for the retina's transient ability to remain healthy in the face of DM.

GSE328962 Type I restriction–modification systems regulate gene expression through DNA topology

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Yasmeen Althari ; Richard D Haigh ; Marco R Oggioni
Series Type : Expression profiling by high throughput sequencing
Organism : Escherichia coli

RNA-seq analysis of wildtype Escherichia coli MG1655 versus a strain with knockout of the hsdM gene of the Type I restriction enzyme EcoKI

GSE328951 The embryonic origins of site-specific arthritis; Bulk RNA sequencing of CD34+(Pi16+) fibroblasts stimulated with TNF and IL1b.

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Sarah Davidson ; Christopher Buckley ; Mark Coles
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

The cellular basis for site-specific inflammation remains unclear. In human fingers, proximal interphalangeal (PIP) joints are preferentially affected by inflammatory arthritis, whereas distal interphalangeal (DIP) joints are spared, providing a model to investigate the predilection of inflammation to distinct sites. We combine single-cell RNA sequencing, imaging and X-ray tomography to examine cellular composition, spatial organization and structure of finger joints during foetal development. PIP joints were enriched for Pi16+ fibroblasts, which are located in perivascular regions and at tendon–ligament interfaces. To investigate whether Pi16+ fibroblasts have a specific response to inflammatory cytokines Pi16+ and Pi16- cells were sorted from foetal fingers using the co-expressed marker CD34. Thes cells were cultured in vitro with and without TNF and IL1b and analyzed using bulk RNA sequencing.

GSE328950 Osteopontin links acquired resistance to hypoxia-inducing antiangiogenics with refractoriness to anti-PD-L1 agents in breast cancer

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Jose L Ruiz-Sepulveda ; María J Bueno ; Silvana Mouron ; Verónica Jiménez-Renard ; Manuel Muñoz ; Manuel Moradiellos ; Leonardo Garma ; Luis García-Jimeno ; Adam Watson ; Ghassan Mouneimne ; Solip Park ; Rebeca Jimeno ; Miguel Quintela-Fandino
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Resistance to antiangiogenics is a major challenge in cancer therapy. These agents can either normalize or exacerbate tumor vascular abnormality and hypoxia. The mechanisms of resistance remain unclear in the latter setting. By integrating data from mouse models and clinical trials, we show that hypoxia-inducing anti-VEGF therapy upregulates programmed cell death ligand 1 (PD-L1), yet fails to sensitize tumors to PD-L1 blockade. Mechanistically, early hypoxic stress triggers epithelial osteopontin (Spp1) production, which recruits monocytes and skews macrophages toward M2 states, suppressing T-cell cytotoxicity. Pharmacologic Spp1 depletion impedes the development of hypoxia, M2 infiltration, restores T-cell activity and enables synergy between antiangiogenics and anti-PD-L1. Genetic dissection – tumor-epithelial Spp1 knockout grafts and bone-marrow chimeras generated by lethal irradiation and reconstitution with Spp1-/- or wild-type hematopoietic donors – show that myeloid Spp1 contributes only marginally compared with epithelial Spp1. These findings identify Spp1 as a central mediator of resistance to hypoxia-inducing antiangiogenics, contribute to a comprehensive model of antiangiogenic resistance, and support Spp1-targeted strategies to personalize immuno/antiangiogenic therapy according to tumor hypoxia.

GSE328885 Liver transcriptomic response to partial hepatectomy in intestinal-specific SIRT1 knockout mice

Tue, 28 Apr 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Liver regeneration following partial hepatectomy (PHx) requires coordinated metabolic and inflammatory responses. Here, we investigated the contribution of intestinal SIRT1 to hepatic transcriptional reprogramming during early regeneration. Intestinal-specific SIRT1 knockout mice (SIRTintKO) and wild-type (WT) littermates were subjected to PHx, and liver tissue was collected at 6 h and 24 h post-surgery. Bulk RNA sequencing was performed to characterize genotype- and time-dependent transcriptional changes. This dataset provides insight into gut–liver axis regulation of early regenerative priming and metabolic adaptation.

GSE328884 Enhancer regulation of OSR2 in mandibular incisor agenesis susceptibility [CUT&Tag]

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Liwen Fan ; Xinyu Zhang ; Ji Mao ; Barbara Vona ; Xinze Xu ; Mulong Du ; Lan Ma ; Yongchu Pan
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens

Mandibular incisors are the most frequently congenitally absent teeth in Asian populations, affecting mastication, speech, aesthetics, and oral and maxillofacial functions over the long term. However, the genetic etiology of mandibular incisor agenesis (MIA) remains obscure. In this study, we conducted the first genome-wide association study on MIA in a Chinese population and identified an enhancer variant rs71514987 associated with an increased risk of MIA (odds ratio = 2.18, 95% confidence interval = 1.83-2.58, P = 3.62×10-19). Functional characterization indicated that rs71514987 C allele reduced the binding affinity of GATA4 to the OSR2 promoter, leading to increased OSR2 expression via remote regulation. Notably, elevated OSR2 levels promoted cell proliferation but diminished cell differentiation, migration, and apoptosis capabilities in stem cells from human exfoliated eciduous teeth (SHED), as well as abnormal development of pharyngeal teeth in zebrafish models. Mechanistic experiments further revealed that OSR2 bound to the promoter region of CXCR4, promoting its transcription level in the GPCR pathway, thereby influencing odontogenic differentiation during tooth development. Our findings provide novel insights into the molecular etiology of MIA.

GSE328878 Transcriptomic comparison of RA vs healthy monocytes undergoing different ex vivo activation conditions

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Shao Thing Teoh ; Anastasiya Börsch ; Bojana Müller-Durovic
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Rheumatoid arthritis (RA) monocytes are primed for inflammatory activation, but their disease-intrinsic molecular features have not been systematically profiled across omics layers. We aimed to define RA-associated alterations in primary human monocytes using an integrated multi-omics approach under controlled differentiation and stimulation conditions. Transcriptomics data showed upregulation of inflammatory and interferon-related programs but downregulation of translation- and mitochondrial matrix-associated gene sets in RA monocytes. Constraint-based metabolic modeling using transcript abundances as proxies for enzyme activities showed widespread downregulation of glycosylation-related metabolic fluxes.

GSE328655 A high-resolution, sex-stratified atlas of transcriptional and alternative splicing dynamics in the fasting mouse liver.

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Jessica M Treeby ; Jean-Michel Fustin ; Benjamin Saer ; Louise A Hunter ; Shin-Yu Kung
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The liver's response to fasting is a fundamental adaptive mechanism, yet its temporal complexity, circadian dimension and sexual dimorphism remain incompletely understood. Here we present a high-resolution transcriptomic atlas of the fasting mouse liver, profiling both male and female C57BL/6 mice every 4 hours across a 36-hour fast initiated at a defined circadian time. Using an integrated framework combining high-resolution time-series analysis with stringent statistical filtering, we identify 2,995 genes organised into eight kinetically distinct clusters that collectively delineate a phased transcriptional transition from acute metabolic remodelling to prolonged nutrient deprivation. Contrary to prior reports, fasting amplifies rather than diminishes circadian transcription, increasing the number of rhythmically expressed genes from 727 to 1,233—indicative of a clock re-gearing rather than clock disruption. Extending our analysis to exon-level quantification reveals that differential exon usage constitutes an independent regulatory layer, targeting processes not captured by transcript abundance alone, including SAM metabolism, ferroptosis and mRNA processing. Circadian rhythmicity in exon usage is demonstrated here for the first time. Sexual dimorphism is pervasive but primarily quantitative, reflecting differences in the magnitude and temporal precision of a conserved programme rather than divergent regulatory logic. This open-access, multi-layered dataset provides a comprehensive resource for the study of nutritional and circadian regulation of liver metabolism.

GSE328540 Full length transcriptome sequencing of rat abdominal aorta primary EC

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : HongFei Zhang ; TongLin Pan ; ZongZe Li ; MingJian Liu
Series Type : Expression profiling by high throughput sequencing
Organism : Rattus norvegicus

MicroRNAs are well established as key regulators of cellular function and viability. A growing body of evidence indicates that multiple miRNAs are involved in the formation and rupture of IAs. MicroRNA-337-3p (miR-337-3p), in particular, has been implicated in the pathogenesis of diverse conditions—including tissue injury, osteoarthritis, and malignancies—by modulating cellular proliferation, fundamental biological processes, and oxidative stress-induced inflammatory responses. The abdominal aorta was excised from rats, with tissue segments everted to reveal the endothelium. Cultured endothelial cells (ECs) were transfected with 100 nM hsa-miR-337-3p inhibitor. RNA sequencing was performed to map the genetic differences lining between the WT and miRNA-337-3p-/- EC.

GSE328481 Uncovering ectopic GC-like niches for tumor reactive lymphocyte priming in lung adenocarcinoma using Stereo-XCR-seq

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Zhan Xiaojuan ; Huang Mengye ; Zhang Yang ; Liu Zhong ; Liu Chengwu ; Guo Yanying ; Liu Yi ; Zhou Wenwen ; Yan Yixin ; Zeng Hui ; Dong Yingqi ; Dong Xuan ; Chen Xiaoyu ; Yang Haohang ; Ma Rong ; Zhu Fan ; Zheng Xubin ; Li Xinxing ; Hou Sen ; Gao Zhidong ; Yin Jinwen ; Chan Francis Ka-ming ; Wu Qin ; Deng Senyi ; Yao Yin ; Suo Shengbao ; Liu Chuanyu ; Liu Longqi ; Xu Xun ; Hou Yong ; Tao Haoran ; Ai Xinlei ; Dong Yuliang ; Zeng Tao ; Sun Hanyong ; Li Young ; Zuo Li ; Wang Hua ; Liu Xin ; Wu Zhifang ; Zhou Jingying ; Zeng Zexian ; Feng Yu
Series Type : Other
Organism : Homo sapiens

This experiment aims to dissect the spatial immune microenvironment of lung cancer by performing Stereo-XCR-seq on fresh-frozen tumor tissues. First, we conduct rigorous sample quality control, perform serial tissue sectioning, use H&E staining for morphological validation, and capture mRNA in situ on Stereo-seq chips. Subsequently, we enrich TCR and BCR transcripts from the constructed Stereo-seq libraries using our in-house developed sscirPCR strategy, via nested PCR-mediated ligating element addition, splint oligo-induced circularization, and two-round specific PCR amplification, enabling the spatial mapping of lymphocyte clonal dynamics within the tumor tissue to uncover immune evasion mechanisms and inform immunotherapeutic strategies.

GSE328107 PI3K Regulates Wild-type RAS Signaling to Confer Resistance to KRAS Inhibition

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Xiangyu Ge ; Jaffarguriqbal Singh ; Wenxue Li ; Cassandra S Markham ; Christian F Ruiz ; Stites C Edward ; Moitrayee Bhattacharyya ; Yansheng Liu ; Mandar D Muzumdar
Series Type : Other
Organism : Homo sapiens

Despite the availability of RAS inhibitors and the dependence of >90% of pancreatic ductal adenocarcinomas (PDAC) on oncogenic KRAS mutations, resistance to KRAS inhibition remains a serious obstacle. We showed here that PI3K plays a major role in this resistance through upstream activation of wild-type RAS signaling – beyond its known KRAS effector function. The combination of proximity labeling, CRISPR screening, live-cell imaging, and functional assays revealed that PI3K orchestrates phosphoinositide-mediated GAB1 recruitment to the plasma membrane, nucleating assembly of RAS signaling complexes that activate MAPK in an EGFR/SHP2/SOS1-dependent manner. Inhibiting PI3K enhanced sensitivity to mutant-specific KRAS inhibitors in PDAC cells, including in cells with clinically identified PIK3CA mutations. These findings refine RAS-PI3K signaling paradigms, reveal that PI3K-driven wild-type RAS activation drives resistance to KRAS inhibition, and illuminate avenues for augmenting KRAS-targeted therapies in PDAC.

GSE326801 Astrocyte-microglia crosstalk via CSF1 and IFNb promotes central nervous system repair

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Tuoxin Cao ; Matin Hemati-Gourabi ; Yongliang Liu ; Anna E Mills ; Lauren Baur ; Ellie P Rice ; Theo Klippel ; Yiwen Yan ; Xiu Xu ; William K Fenske ; Jean X Jiang ; Meifan Chen
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Despite accumulating evidence of functional interactions between astrocytes and microglia in central nervous system (CNS) injury and disease, mechanisms coordinating their response to CNS insults remain incompletely understood. We report that injury-reactive astrocytes at the lesion border upregulate colony stimulating factor 1 (CSF1) required for microglial proliferation, wound closure, and motor recovery after focal spinal cord injury. Intriguingly, astrocyte-targeted deletion of CSF1 also reduces cell number of border-forming astrocytes, revealing positive feedback regulation between astrocytes and microglia. We further show that microglia produce interferon ? (IFN?), which reciprocally supports astrocyte survival. Genetic disruption of interferon signaling in astrocytes in turn impairs astrocytic border formation, coordination with microglia in wound healing, and motor recovery. This work uncovers astrocyte-microglia crosstalk via CSF1 and IFN? that synergizes the acute injury response of these cells for neural repair, providing insights into fundamental biology of astrocyte-microglia communication and its therapeutic potential.

GSE324408 Single-cell transcriptional landscape of muscle-derived stem/progenitor cells reveal hallmarks of aging and rejuvenation

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Kavitha Mukund ; Seth D Thompson ; Chelsea L Rugel ; Kamil K Gebis ; Richard L Lieber ; Jeffrey N Savas ; Shankar Subramanium ; Mitra Lavasani
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Muscle-derived stem/progenitor cells (MDSPCs) are an adult stem cell population with demonstrated regenerative and rejuvenative potential distinct from other muscle progenitor cells. However, their molecular identity and developmental status remain poorly defined. Using single-cell transcriptomic and proteomics, we profiled murine MDSPCs comprehensively across age groups. We show that MDSPCs exist along a transcriptional continuum of maturation—ranging from metabolically active, proliferative early-stage cells to late-stage, lineage-committed myogenic populations. While lacking canonical pluripotency markers, early-stage MDSPCs express gene programs associated with embryonic progenitor identity, suggesting a non-canonical, multipotent-like state. These features distinguish them from both satellite cells and committed myoblasts. Aging reshapes this continuum by reducing stemness-associated signatures while enhancing differentiation programs and oxidative stress. The identification of distinct MDSPC states provide critical insights into mechanisms that underly tissue regeneration and aging. These analyses offer a blueprint for development of future regenerative therapies to combat age-related functional decline.

GSE323377 New Insights into Müllerian duct differentiation provided by single cell transcriptomics in the chicken embryo

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Juan Lan Tan ; Adele Barugahare ; Andrew Thomas Major ; Craig Allen Smith
Series Type : Expression profiling by high throughput sequencing
Organism : Gallus gallus

In vertebrate embryos, Müllerian ducts give rise to the female reproductive tract. Aberrations in duct development cause reproductive disorders, many of which have an unknown etiology. Here, we present a comprehensive analysis of Müllerian duct differentiation using single cell transcriptomics in the chicken embryo, a unique model for duct development. The data reveal greater cellular complexity of Müllerian duct differentiation than previously understood. Duct mesenchyme has two transcriptionally distinct populations, while duct epithelium shows distinct regionalised compartments. Trajectory analysis shows that these populations have different fates. Single cell transcript profiling of the regressing male mesenchyme identifies new genes implicated in duct regression. One of these male-restricted transcripts, DKK4, responds to Anti-Mullerian Hormone induction and can induce duct regression when ectopically expressed in females. Lastly, the right female duct does not regress in the same manner as in males, being transcriptionally distinct. These data provide new insights into Müllerian duct differentiation.

GSE319569 An Epigenetic Progeria Links Hypermethylation to Age-Related Pathology

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Tomoya Isobe ; Berthold Gottgens ; Andrew P Jackson
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Declining tissue function and regenerative capacity underlie many chronic diseases.Experimentally establishing the mechanistic basis for such tissue ageing presents substantial challenges, given decades-long timescales and multifactorial origins. Epigenetic alterations have been proposed to have a key aetiological role, but whether they are correlative or causal remains a key unanswered question, as does their contribution to specific age-related pathologies. Here, we establish a novel epigenetically-driven accelerated ageing syndrome. We demonstrate that DNMT3A gain-of-function mutations in Heyn-Sproul-Jackson syndrome recapitulate age-related gains in DNA methylation, cause multilineage stem cell dysfunction, and phenocopy aspects of ageing in humans and mice. We also show that region-specific DNA hypermethylation at lineage-specific genes can explain reduced stem cell output and lineage skewing. Hence, starting from a Mendelian disorder, we causally implicate DNA methylation-mediated stem cell exhaustion in the aetiology of medically important age-related haematological, bone and metabolic pathologies, that might be targetable by future therapies.

GSE319376 A distinct CD38+CD45RA+ population of CD4+, CD8+ and double-negative T cells is controlled by FAS [alps]

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Maria E Maccari ; Geoffroy Andrieux ; Anne Rensing-Ehl ; Melanie Boerries
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

The identification and characterization of rare immune cell populations in humans can be facilitated by their growth advantage in the context of specific genetic diseases. Here, we use autoimmune-lymphoproliferative syndrome to identify a population of FAS-controlled TCRab+ T cells. They include CD4+, CD8+ and double-negative T cells and can be defined by a CD38+CD45RA+T-BET- expression pattern. These unconventional T cells are present in all healthy individuals, generated before birth, enriched in lymphoid tissue and do not expand during acute viral infection. They are characterized by a unique molecular signature that is unambiguously different from other known T-cell differentiation subsets and independent of CD4 or CD8 expression. Functionally, FAS-controlled T cells represent highly proliferative T cells with IL-10 cytokine bias. Moreover, FCT are as highly glycolytic as EBV-induced effector T cells but their metabolic program is uncoupled from T-bet expression and IFNg production. Mechanistically, regulation of this physiologic population is mediated by FAS and CTLA4 signaling and its survival is enhanced by mTOR and STAT3 signals. Genetic alterations in these pathways result in expansion of FAS-controlled T cells, which can cause significant lymphoproliferative disease.

GSE318853 Highly regional generation and heterogenous differentiation of basal cells in mouse trachea

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Xiuxiu Liu ; Wendong Weng ; Zhen He ; Kuo Liu ; Maoying Han ; Bin Zhou
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The airway epithelium comprises three major cell types: basal cells, secretory cells, and ciliated cells. Among these, basal cells serve as stem cells to generate other cell types. Airway basal cells have been recognized as functionally heterogeneous, with numerous studies with specific cell markers. The regional heterogeneity of basal cells has yet to be fully addressed, despite there being some in vitro evidence. In this study, we utilized a proliferation tracing system to demonstrate regional heterogeneity in the proliferative capacity and differentiation of airway basal cells. We found that dorsal basal cells possess a significantly higher proliferative capacity compared to their ventral counterparts. Further analysis revealed that the proliferating basal cells primarily constitute a subset previously identified as multipotent basal stem cells, which undergo symmetric division to expand the stem cell pool. Furthermore, we identified that the canonical Wnt signaling pathway plays a crucial role in maintaining the proliferation of these multipotent basal cells. These findings may have important implications for understanding airway repair mechanisms in disease and injury.

GSE317003 Epigenetic and transcriptional alterations in Kmt2c/Kmt2d-deficient gastric cancer [ChIP-Seq]

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Dan Li ; Naitao Wang ; Yu Chen
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

KMT2C and KMT2D are two of the most frequently mutated genes in gastric adenocarcinoma, yet their function in cancer initiation remains poorly understood. In this study, we developed mouse models to investigate the molecular mechanism of Kmt2c/d loss in gastric tumorigenesis.

GSE316994 Epigenetic and transcriptional alterations in Kmt2c/Kmt2d-deficient gastric cancer [RNA-seq]

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Dan Li ; Naitao Wang ; Yu Chen
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

GSE316892 The Gene Regulatory Evolution of the Human Skeleton (human-chimp and human-gorilla hybrid cells)

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Yizhi Yan ; Nadav Mishol ; Katharina Lange ; Zicong Zhang ; Gal Bodek ; Itamar Nini ; Noam Priel ; Omer Ronen ; Nachshon Egyes ; Aya Kigel ; Amit Philosoph ; Liat Rotenstreich ; Adi Rozenblatt ; Lucas E Wange ; Guy Hirsh ; Sergey Viukov ; Idan Korenfeld ; Ariel Afek ; Yaqub Hanna ; Assaf Marom ; Simon Fishilevich ; Martin Kuhlwilm ; Tomas Marques-Bonet ; Fumitaka Inoue ; David Gokhman
Series Type : Expression profiling by high throughput sequencing
Organism : Gorilla gorilla ; Homo sapiens ; Pan troglodytes

This GEO submission accompanies the RNA-seq data of human-chimp and human-gorilla hybrid cells in the study “The Gene Regulatory Evolution of the Human Skeleton”. Changes in gene regulation are key drivers of human evolution. However, which regulatory changes shaped human adaptations, and especially how, remains largely unknown. Skeletal alterations have been particularly central in human evolution, facilitating upright locomotion and large brains, and influencing child- birth and our distinctive faces. Here, we generated human-chimp and human-gorilla hybrid osteochondral progenitor cells to study the cis-regulatory expression changes that distinguish humans from other great apes. We identified 4152 chimpanzee-specific, and 4463 human-specific cis-regulatory expression changes.

GSE316891 The Gene Regulatory Evolution of the Human Skeleton (Massively parallel reporter assay (MPRA))

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Yizhi Yan ; Nadav Mishol ; Katharina Lange ; Zicong Zhang ; Gal Bodek ; Itamar Nini ; Noam Priel ; Omer Ronen ; Nachshon Egyes ; Aya Kigel ; Amit Philosoph ; Liat Rotenstreich ; Adi Rozenblatt ; Lucas E Wange ; Guy Hirsh ; Sergey Viukov ; Idan Korenfeld ; Ariel Afek ; Yaqub Hanna ; Assaf Marom ; Simon Fishilevich ; Martin Kuhlwilm ; Tomas Marques-Bonet ; Fumitaka Inoue ; David Gokhman
Series Type : Other
Organism : Homo sapiens ; synthetic construct

This GEO submission accompanies the massively parallel reporter assay (MPRA) data in the study “The Gene Regulatory Evolution of the Human Skeleton”. Changes in gene regulation are key drivers of human evolution. However, which regulatory changes shaped human adaptations, and especially how, remains largely unknown. Skeletal alterations have been particularly central in human evolution, facilitating upright locomotion and large brains, and influencing child- birth and our distinctive faces. Here, we employed MPRAs in key skeletal cells - chondrocytes - to uncover the functional role of the 574,290 enhancer and promoter substitutions that distinguish humans from their ape relatives. Using this atlas, we identified 15,077 sequences whose activity has diverged since our split from chimpanzees.

GSE314244 Inhibition of oogenic JNK prevents primary ovarian insufficiency and infertility induced by DNA-damaging anti-cancer agents

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Wenlong Zhao ; Jiyang Zhang ; Yingnan Bo ; Yingzheng Wang ; Yunman Song ; Qiang Zhang ; So-Youn Kim ; Shuo Xiao
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Primary ovarian insufficiency (POI) and related infertility, early menopause, and endocrine disorders are major side effects in young female cancer patients undergoing cancer treatment. Current strategies preserving ovarian functions and fertility can be suboptimal due to concerns of feasibility, efficacy, or safety. Herein, we identify c-Jun N-terminal kinase (JNK) as a pivotal factor regulating the DNA damage response (DDR) signaling in oocytes of primordial follicles in response to DNA-damaging chemotherapy. Using pharmacological inhibition of JNK and a mouse model with oocyte-specific deletion of JNK, together with bioinformatic, molecular, and computational approaches, we show that inhibition of oogenic JNK prevents chemotherapy-induced oocyte apoptosis and POI as well as preserve long-term reproductive cycles and fertility. Mechanistically, JNK is activated upon chemotherapy-induced DNA damage in oocytes of primordial follicles, which further activates the transcription factor TAp63α and triggers oocyte apoptosis. we further used a breast cancer mouse model to demonstrate that JNK inhibition preserves the ovarian reserve without interfering with the anti-cancer efficacy of chemotherapy. Together, our research establishes JNK as a crucial determinant of oocyte apoptosis and POI following DNA-damaging cancer therapy, highlighting JNK as a promising target for developing ovarian protectant and preserving the ovarian reserve, fertility, and ovarian endocrine functions in young female cancer patients.

GSE314056 Tbx16 and mesogenin 1 promote presomitic mesoderm differentiation by repressing the mesodermal progenitor cell state

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Guoyu Zhu ; Miriam A Genuth ; Yanrong Xiao ; Abigail A Kindberg ; Kayleigh Hackett ; Scott A Holley
Series Type : Expression profiling by high throughput sequencing
Organism : Danio rerio

During zebrafish embryonic body elongation, differentiation of mesodermal progenitors into presomitic mesoderm requires the transcription factors tbx16 and mesogenin 1. Here, we elucidate how these genes promote differentiation. We use temporally controlled tbx16 and mesogenin 1 overexpression and RNAseq to identify immediate downstream changes in gene expression. Using machine learning and game theory, we integrated differentially expressed genes with wild-type scRNAseq data and identified genes downstream of tbx16 and mesogenin 1 during mesoderm differentiation. This data-driven analysis indicates that mesogenin 1 and tbx16 primarily repress expression of genes as mesodermal progenitors differentiate. Strikingly, the genes that are most important for defining transcriptional cell states during mesoderm differentiation are most strongly repressed by tbx16 and mesogenin 1. Moreover, these downstream effectors are enriched for genes with known roles in mesoderm development and body elongation such as Fgf, Wnt and Bmp pathways and the transcription factors tbxta, eve1, hoxd12a, hoxd13b, lef1, cdx4, tbx16l, ved, vent and vox. Gradients of Fgf and Wnt specify the mesodermal progenitor state in the posterior tailbud and activate many of these transcription factors indicating that tbx16 and mesogenin 1 promote mesoderm differentiation by repressing this progenitor state.

GSE312942 Inhibition of METTL3 by STC-15 induces RNA misprocessing that results in dsRNA formation and activates innate immunity [RNA-seq]

Tue, 28 Apr 2026 00:00:00 -0400

Contributor : Harry Fischl
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

The RNA methyltransferase METTL3 is responsible for the generation of m6A, the most abundant modification mark on mRNA and long non-coding RNA. Accumulating evidence suggests numerous roles of METTL3 in cancer initiation and progression and highlights the potential for targeting this enzyme in oncology. STC-15 is a potent and selective METTL3 inhibitor and the first RNA modifying enzyme inhibitor to enter human clinical development. It is structurally related to the previously published tool inhibitors STM2457 and STM3675. We previously identified the induction of a cancer cell-intrinsic interferon response following pharmacological inhibition of METTL3, leading to activation of T-cell-mediated anti-tumour response. Here, we profiled m6A levels at nucleotide resolution using GLORI and characterised RNA changes following METTL3 inhibition with STC-15 or STM3675. Following loss of m6A, we uncovered aberrant mRNA transcripts arising from intron retention (IR) and transcriptional run-on (RO) events downstream of m6A-enriched exons in human cancer cells and in tumour samples in vivo. We found that these IR and RO events produce double-stranded RNA and are bound by the cytoplasmic dsRNA sensor MDA5.Using preclinical in vitro and in vivo models, we characterised in detail the anti-tumour immune responses induced by STC-15. Our study reveals how METTL3 inhibition leads to dsRNA accumulation, which triggers a type I interferon response and induces anti-tumour immunity. Together, these findings provide a mechanistic rationale for STC-15 as a novel anti-cancer drug both as monotherapy and in combination with anti-PD1 checkpoint inhibitors.

GSE309074 Arginine deprivation of ASS1-deficient cancers drives mistranslation and neoepitope production

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Remco Nagel ; Adva Kochavi ; Karine Flem Karlsen ; Mrittika Adhikary ; Yali Gal-On ; Maria Klaoudatou ; Julien Champagne ; Lorenzo Valcanover ; Heyilimu Palashati ; Morten M Nielsen ; Xiaodong Feng ; Pierre-Rene Körner ; Lisanne Giebel ; Weiwen Yang ; Arno Velds ; Liesbeth Hoekman ; Onno B Bleijerveld ; Olaf van Tellingen ; Johanna Olweus ; Reuven Agami
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Arginine biosynthesis is frequently suppressed in cancer due to loss of ASS1 expression, rendering cancer cells reliant on extracellular arginine. This feature has propelled the development of systemic arginine depletion strategies, which are clinically safe but have limited clinical benefit. Here, we demonstrate that in conditions of arginine scarcity, cancer cells with low ASS1 expression resort to aberrant mRNA translation in the form of ribosomal frameshifts and amino acid misincorporations. While aberrant proteins originated from most arginine codons, the predominant effect was observed at AGA. This codon preference is caused by a selective decrease in tRNAArg(UCU) levels after arginine deprivation, linked to METTL1-mediated tRNA-modification. Using proteomics and immunopeptidomics, we validated that arginine shortage induces aberrant protein production at the endogenous level. We further demonstrate that such inducible neopeptides are immunogenic, laying the foundation for improved cancer therapy combining systemic arginine depletion strategies with T-cell receptor-based targeting of non-classical neoantigens.

GSE309063 Arginine deprivation of ASS1-deficient cancers drives mistranslation and neoepitope production [Ribo-Seq]

Tue, 28 Apr 2026 00:00:00 -0400

GSE301598 Comparative single-cell transcriptomic analysis of human primary and stem cell-derived islets under acute hypoxia

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Kameron Bradley ; Matthew Ishahak ; Jeffrey R Millman ; Camryn Moore ; Marlie M Maestas ; Daniel A Veronese-Paniagua
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

To understand the divergent responses of different islet sources to the hypoxic stress encountered post-transplantation, we performed a direct, comparative single-cell RNA sequencing analysis of human primary islets and stem cell-derived islets (SC-islets, HUES8 line) over an acute time course (0, 6, 24, and 48 hours) of hypoxic exposure (1% O2). Our data reveal that while both islet types activate conserved core stress pathways, they subsequently execute markedly divergent adaptive strategies. Primary β-cells navigate hypoxia through a profound suppression of their mature identity and a shift towards a quiescent, energy-conserving state. In contrast, SC-β cells mount a highly plastic and metabolically dynamic response that is coupled with significant lineage instability and functional dysregulation. These findings highlight fundamental, source-specific differences in hypoxic adaptation, providing a rich resource for developing tailored strategies to improve islet transplantation success.

GSE301098 Gene expression analysis in hepatocytes in response to hepatocyte-specific Succinate Receptor 1 (SUCNR1) deletion

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Anna Díez-Villanueva ; Sonia Fernández-Veledo
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The liver plays a crucial role in metabolic adaptations in response to nutrients, a function that is critically dependent on its zonated structure. Succinate, a key intermediate of the tricarboxylic acid cycle, has emerged as a postprandial signaling metabolite that regulates metabolic adaptations to food intake in adipose tissue and pancreatic beta cells through its receptor SUCNR1. Considering that SUCNR1 is also expressed in hepatocytes, we hypothesized a role for the succinate-SUCNR1 axis in liver metabolic homeostasis. To better understand the role of Sucnr1in hepatocytes, we generated a mouse model specifically lacking Sucnr1 in hepatocytes (Hep-Sucnr1 KO mice) and performed an RNA-seq of isolated hepatocytes from controls (Sucnr1 fl/fl mice) and Hep-Sucnr1 KO mice.

GSE300875 Mitochondrial toxins cause widespread downregulation of pathways in X-linked dystonia-parkinsonism patient-derived neurons

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Karen Grütz ; Axel Künstner ; Hauke Busch ; Christine Klein ; Philip Seibler
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

The genetic mechanism underlying the neurodegenerative movement disorder X-linked dystonia-parkinsonism (XDP) involves a retrotransposon insertion within the TAF1 gene. TAF1 encodes the TATA-box binding protein-associated factor 1, the largest subunit of the basal transcription factor TFIID, which connects transcription activation to the assembly of the RNA polymerase II preinitiation complex at the core promoter of genes. This study investigated how the TAF1 mutation affects the transcriptomes of XDP patient-derived neurons under basal conditions and in response to mitochondrial toxins.

GSE300723 Progressive cell fate specification in morphallactic regeneration [scRNA-seq]

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Clara Nuninger ; Panagiotis Papasaikas ; Sebastien Smallwood ; Jacqueline Ferralli ; Charisios Tsiairis
Series Type : Expression profiling by high throughput sequencing
Organism : Hydra vulgaris

Through regeneration variable species replace lost parts of their body. This is achieved either by growth of new structures at the amputation side (epimorphosis), as is the case of axolotl limb regeneration, or through remodeling of the remaining tissue (morphallaxis), as happens in Hydra. Whereas work on epimorphic regeneration support a gradual proximal to distal establishment of cell identities, morphallactic regeneration is believed to rely on initial establishment of boundary conditions that organize the adjustment of the pattern. Performing single cell RNA sequencing during regeneration in Hydra, we revealed the sequence of cells’ transdifferentiation into the missing identities. We provide evidence that morphallaxis proceeds with progressive specification of cell fates, unifying its mechanism with the one found for epimorphosis.

GSE300721 Progressive cell fate specification in morphallactic regeneration [RNA-seq]

Tue, 28 Apr 2026 00:00:00 -0400

GSE299374 Meningioma cell reprogramming and microenvironment interactions underlie brain invasion

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Youngblood Mark W ; Aggarwal Ayush ; Raleigh David
Series Type : Other
Organism : Homo sapiens

Meningiomas brain invasion encumbers resection and increases the risk of tumor recurrence, but the molecular mechanisms underlying meningioma brain invasion are poorly understood. To identify molecular and cellular features of brain-invasive meningiomas, we performed spatial transcriptomic of brain-invasive meningiomas. Our results reveal that meningioma brain invasion is defined by molecular remodeling of tumor cells and functional interactions within the tumor microenvironment.

GSE299284 Fucosyltransferase 4-derived Peptide Bioconjugates on Carbon Nanotubes Enhance Antitumor Immunity in an Ovarian Cancer Mouse Model

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : José Jesús Guzmán-Mendoza ; Blanca Sánchez-Ramírez ; Patricia Talamás-Rohana
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

This study explored the potential of carbon nanotubes (CNTs) bioconjugated with antigenic epitopes from fucosyltransferase 4 (FUT4) to serve as adjuvants and carriers in ovarian cancer immunotherapy. We confirmed FUT4 overexpression via flow cytometry and confocal microscopy in an immunocompetent ovarian cancer model in which the ID8-Def29/Vegf-a cell line (ID8DVLuc) was inoculated into C57BL6 mice. Mice were immunized with nonconjugated peptide (PEP37), PEP37 bioconjugated CNTs (f-CNTs), or f-CNTs plus adjuvant, and nonimmunized mice were used as controls. Tumor development, the spleen, and ascitic fluid immune populations, the antibody response, and survival rates were evaluated. The results revealed reduced tumor development and ascitic fluid volume in immunized mice, with the best outcomes in the f-CNT group. Immunized mice presented increased infiltration of leukocytes, M1 macrophages, dendritic cells, T lymphocytes, and CD8+ T cells alongside reduced Tregs. Enhanced IgM, IgG1a, and IgG2a responses were observed in the f-CNT groups. Splenocytes from these groups also showed increased antigen-specific proliferation and enhanced cytotoxicity against ID8DVLuc cells mediated by CD8+ T cells. Survival analysis revealed median survival times of 6, 7.5, 11, and 8.5 weeks for the nonimmunized, PEP37, f-CNT, and f-CNT plus adjuvant groups, respectively. In addition, RNA-seq analysis of f-CNT-immunized mice revealed the overexpression of genes related to antigen processing and presentation, CD8+ T-cell activation, and Th1-type-mediated responses (H2-K1, H2-D1, B2m, Trex1 Cd80, Cd8a, Prf1, IL18r1, Ccr7, Stat4, Tbx21), among others. These findings suggest that f-CNTs enhance the antitumor immune response mediated by M1 macrophage polarization, enhance antigen processing and presentation to CD8+ T cells, and evoke a robust cytotoxic response against ID8DVLuc cells. These findings suggest the potential of this nanocarrier system in ovarian cancer immunotherapy

GSE298951 Autoimmune antibody-induced neuronal hyperactivity triggers pathological Tau in IgLON5 disease

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Bilge Askin ; Pia Grundschoettel ; Thomas Ulas ; Susanne Wegmann
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Anti-IgLON5 disease is an autoimmunity/neurodegeneration overlap disorder in which autoantibodies (AABs) against the neuronal cell surface protein IgLON5 lead to profound brain dysfunction. Brains of patients show Tau pathology, neuroinflammation, and neurodegeneration in multiple brain regions. Through administering patient-derived α-IgLON5 AABs to mice and cultured neurons, we here deciphered the cellular mechanisms of Tau pathology and neurodegeneration in α-IgLON5 disease, highlighting a central role of neuronal activity modulation in the disease pathology. Pathogenic human α-IgLON5 AABs induced acute neuronal hyperactivity, which triggered Tau changes typically found early in Tau-related neurodegenerative diseases like Alzheimer’s disease (AD). α-IgLON5 AAB-induced Tau phosphorylation and somatodendritic resorting selectively occurred in key hippocampal connections, involving dentate gyrus granule cells, mossy fiber projections and commissural fiber tracts. These changes were accompanied by a Tau-specific neuroinflammatory response, involving the complement pathway, microglial MHC class II proteins, T cell receptors, and deregulation of synaptic activity and cell-cell interactions. These findings provide new insights into the origin of autoimmune-triggered α-IgLON5 disease pathology and highlight that, similar to recent reports in AD patients, neuronal hyperactivity may be a disease-overarching driver of Tau pathology.

GSE298744 Genetic Deletion of the Inflammatory Bowel Disease -Associated Risk Gene Rgs14 Aggravates Experimental Colitis

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Jan Niess ; Mao Chen ; Florian Geier
Series Type : Expression profiling by high throughput sequencing ; Other
Organism : Mus musculus

Regulators of G protein signaling (RGS) deactivate G protein-coupled receptors (GPCRs), one of the most prominent receptor families with diverse functions. Of the twenty RGS, Rgs14 single-nucleotide polymorphism is associated with inflammatory bowel disease. This manuscript describes a novel conditional mouse line that allows deletion of Rgs14 in defined cell lines. We show that deletion of Rgs14 in macrophages affects macrophage function and aggravates colitis severity. This novel conditional mouse model will help to investigate further the function of Rgs14 for inflammatory bowel disease and possibly other conditions, such as metabolism, neuroscience, and aging

GSE298538 Pax6 deficiency results in expansion of dysfunctional limbal epithelial stem cells

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Nihal Kaplan ; Parisa Foroozandeh ; Tsutomu Kume ; Robert M Lavker ; Han Peng
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

we took advantage of PAX6 +/- mice and utilized single cell RNA sequencing to characterize the abnormalities in PAX6 +/- mouse corneas at the single cell level.

GSE298032 Host-Directed Antiviral Activity of SB2960 Through Selective Induction and Remodeling of Stress Granules

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Wan Gi Byun ; Sumin Son ; Meehyun Ko ; JinAh Lee ; Songrui Zhao ; Ju Hee Kim ; Kannan Vaithegi ; Jung Ho Lee ; Dawon Yi ; Peng Zou ; Seungtaek Kim ; Seung Bum Park
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

The increasing prevalence of emerging infectious diseases highlights the urgent need for broad-spectrum antiviral therapeutics. Here, we report the discovery of SB2960, a small molecule that promotes stress granule (SG) formation and exhibits potent antiviral activity across diverse viral species. Here, we applied genetically-encoded photosentisizer miniSOG induced RNA labeling technique CAP-seq to profile RNA components in SG induced by poly(I:C) and drug SB2960 to investigate how SB2960 modulates the RNAs composition of SGs.

GSE297745 IL-17A Neutralization Prevents Immune Checkpoint Inhibitor-Associated Myocarditis and Synergistically Enhances Immune Checkpoint Blockade Therapy

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Stephen T. C. Wong ; Kun Han ; Yin Zheng ; Lin Wang ; Yuanyuan Zhu
Series Type : Other
Organism : Mus musculus

Immune checkpoint inhibitor (ICI)-associated myocarditis is a severe and often fatal immune-related adverse event observed in cancer immunotherapy. To investigate its pathogenesis and prevention, we performed spatial transcriptomics on cardiac tissue from mice treated with dual ICIs (anti–PD-1 and anti–CTLA-4) with or without IL-17A neutralizing antibody. Our analysis revealed immune-mediated fibrotic remodeling and distinct spatial immune cell distributions, providing insights into how IL-17A blockade mitigates cardiac toxicity without compromising immune activation.

GSE296725 Unbiased niche labeling maps immune-excluded niche in bone metastasis

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Xu Zhan ; Liu Fengshuo ; Zhang Xiang
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Microenvironment niches determine cellular fates of metastatic cancer cells. However, robust and unbiased approaches to identify niche components and their molecular profiles are lacking. We established Sortase A-Based Microenvironment Niche Tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastatic colonization. SAMENT was applied to multiple cancer models colonizing the same organ and the same cancer to different organs. Common niche features include macrophage enrichment and T cell depletion. Macrophage niches are phenotypically diverse in different organs. In bone, niche macrophages express estrogen receptor (ER) and exhibit active ER signaling in male and female hosts. Conditional knockout of ER in macrophages significantly retarded bone colonization by allowing T cell infiltration. ER expression was also discovered in human bone metastases of both genders. Collectively, we identified a unique population of ER+ macrophages in metastatic niche and functionally tie ER signaling in macrophages to T cell exclusion during metastatic colonization.

GSE295790 Piezo1 mediates the growth of myoblasts in a microgravity environment

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Yizhou Liu ; Xiaojian Cao ; Danxia Huang ; Hongmei Luo ; Hong Chen
Series Type : Other
Organism : Mus musculus

Skeleton muscle atrophy during prolonged spaceflight poses a significant health challenge for manned space missions, with its underlying molecular mechanisms remaining incompletely understood, particularly regarding how microgravity affects skeletal muscle through mechanotransduction pathways. This study investigates the pivotal role of mechanosensitive Piezo1 channels in myoblast regeneration. Utilizing a two-dimensional clinostat to simulate microgravity and integrating multi-dimensional approaches including 3D genomics and cellular dynamics analysis, we systematically revealed that microgravity promotes C2C12 myoblast proliferation via Piezo1 activation while inducing 3D chromatin structural remodeling. This work pioneers in elucidating a novel mechanism where aberrant mechanotransduction leads to chromatin conformation dysregulation and subsequent skeleton muscle atrophy, providing theoretical foundations and innovative directions for developing mechanobiology-based countermeasures.

GSE295356 Nociceptor clock genes control excitability and pain perception in a sex and time-dependent manner

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Amanda M Zacharias ; Courtney A Bannerman ; Qingling Duan ; Nader Ghasemlou
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Nociception is critical for pain perception and survival and begins with the activation of nociceptors, specialized sensory neurons located in the dorsal root ganglia (DRGs). Both sex and circadian rhythms, governed by clock genes, seem to play a significant role in modulating pain perception. However, the potential interaction between circadian rhythms and sex differences in nociception at the peripheral level has been largely overlooked. Here, we first report that DRGs from mice express clock genes in a time- and sex-dependent manner. Using whole-cell recordings in whole-mounted DRGs and optogenetic stimulation of Nav1.8-expressing neurons, we demonstrate that male nociceptors exhibit reduced excitability during the night, while female nociceptor excitability remains stable across time points. Disruption of the core clock gene Bmal1 in Nav1.8-expressing neurons not only diminished nociceptor activity but also abolished the nighttime reduction in heat sensitivity, highlighting a pivotal role for the molecular clock in regulating nociception. Transcriptomic analyses, voltage-clamp recordings, and pharmacological experiments identified the voltage-gated chloride channel ClC-2, controlled by Bmal1, as a key mediator for the observed fluctuations in male nociceptor excitability. This work opens new avenues for chronobiology-inspired strategies in pain management tailored to sex-specific mechanisms.

GSE294780 Identification of a novel interleukin-9 receptor complex in non-hematopoietic cells

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Cherry CL Cheung ; Mark H Kaplan
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Beyond cell-cell contact, communication at a distance requires the secretion of cytokines that bind to specific receptors on responsive cells. Interleukin (IL)-9 is a cytokine with pleiotropic effects not only on immune cells that contribute to the progression of tumor and autoimmunity, but also on structural cells including airway and intestinal epithelial cells involved in the development of inflammatory and allergic diseases. Typically, IL-9 receptor (IL-9R) functions as a complex of two subunits – the α-chain (IL-9Rα) and a common γ (γc) chain, that is shared with other cytokine receptors. Although structural cells express IL-9Rα, they lack expression of the γc chain. Thus, it is still unclear how IL-9 transmits a signal through a single IL-9Rα chain in non-hematopoietic cells. This study aimed to explore the possibility that like the type II IL-4Rα, the IL-9Rα chain can pair with the IL-13Rα1 chain, forming a type II IL-9R and can mediate IL-9 responses in epithelial cells. We demonstrated that the IL-9Rα /IL-13Rα1 complex was detected in situ in mouse tracheal epithelial cells and human small airway epithelial cells (SAEC) using proximity ligation assay. STAT3 was activated after exposure to IL-9 in vitro in SAEC when co-cultured with neutralizing antibody targeting γc chain but STAT3 activity returned to its basal level in the presence of anti-IL-13Rα1 antibody, providing further evidence of a type II IL-9R on epithelial cells. Strikingly, asthma-associated genes are upregulated in SAEC upon IL-9 stimulation in RNA-seq analysis. Collectively, our results identify a putative receptor complex - a type II IL-9R composed of IL-9Rα and IL-13Rα1, providing a mechanism for responses of structural cells to IL-9 and a potential role in asthma.

GSE294165 Folic acid drives metabolic reprogramming to alleviate Toxoplasma gondii antigen-induced vascular injury

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Jingfan Qiu ; Yingyi Quan ; Jiang Jiang ; Nan Gao ; Jing Guo ; Wei Shi ; Linfeng Jiang ; Chenlu Shao ; Yang Yang
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Infection with parasites is usually accompanied by vascular problems. To investigate the detrimental effects of parasites on blood vessels. We used Toxoplasma gondii (T. gondii), a prevalent intracellular parasite with the potential to induce vascular damage, as an example. In addition to a murine model, a novel human pluripotent stem cell-derived blood vessel organoid (VO) model was emoployed to examined the effect of T. gondii antigens on vessels. We found that T. gondii antigen-induced vascular injury is correlated with inflammation, cellular apoptosis, degradation of extracellular matrix, and disruption of cellular tight junctions. T. gondii antigens also promotes the phenotypic transition of smooth muscle cells (SMCs) from contraction phenotype to secretion phenotype. Interestingly, we found that prophylactic addition of folic acid (FA) appears to counteract all such effects, partially restoring vascular homeostasis. Previous studies on the protective effects of FA on blood vessels remains in its infancy. To reveal the mechanism of FA-mediated vasoprotective effects, we performed transcriptomic and metabolomic analyses. The results show that T. gondii antigen disrupts several vital metabolic pathways crucial for vessel function. Significantly, FA alleviates these metabolic disorders. The protective effect of FA is associated with vascular metabolic reprogramming. This study not only elucidates the mechanisms underlying T. gondii antigen-induced vascular injury, but also reveals a metabolic regulatory role of FA in vascular repair, which has potential value in clinical applications. Additionally, VOs derived from human stem cells are amenable systems for modelling and identifying the regulators and drugs of vascular injury.

GSE288762 Impact of Histone Hypercetylation on genome organization

Tue, 28 Apr 2026 00:00:00 -0400

Contributor : Yu Liu
Series Type : Genome binding/occupancy profiling by high throughput sequencing ; Other
Organism : Homo sapiens

We systematically examined the impact of HDAC inhibitor on genome organization by Hi-C and ChIP-seq

GSE288365 Molecular Drivers of Neuroinflammation in Amyotrophic Lateral Sclerosis

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Zhang Ziyang ; Gate David
Series Type : Other
Organism : Homo sapiens

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron (MN) degeneration in the brain and spinal cord. Although neuroinflammation is increasingly recognized as a hallmark of ALS, the precise molecular programs linking immune responses to MN pathology remain poorly defined. Using an integrated approach that combines single-cell and bulk RNA sequencing with spatial proteogenomics, we characterized both shared and distinct immune dynamics in peripheral blood and spinal cord tissues from sporadic ALS patients and patients carrying C9orf72 repeat expansions. Our analysis revealed broad immune remodeling in C9orf72-ALS, ALS subtype-specific and progression-associated differences in monocyte activation, and antigen-experienced CD8 effector memory T cells with clonal features consistent with antigen-driven responses. Spatial mapping revealed complement activation and lipid-programmed myeloid states converging at sites of MN loss and TDP-43 pathology. Together, these findings connect peripheral and central immune alterations to ALS heterogeneity and highlight stratified immunomodulation as a potential therapeutic strategy.

GSE287341 Dynamic Reprogramming of Stromal Pdgfra-expressing cells during WNT-Mediated Transformation of the Intestinal Epithelium [Figure 5]

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Oscar Pellon-Cardenas ; Prateeksha Rout ; S Hassan ; E Fokas ; Ping He ; I Patel ; J Patel ; O Plotsker ; A Wu ; R Kumar ; M Akther ; Alexandra Logerfo ; S Wu ; DE Wagner ; D Boffelli ; KD Walton ; E Manieri ; Kevin Tong ; Jason R Spence ; NJ Bessman ; RA Shivdasani ; Michael P Verzi
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Stromal fibroblasts of the mesenchyme regulate critical signaling gradients along the crypt-villus axis1 and provide a niche that supports intestinal stem cells in the intestine. Here we report that Pdgfra-expressing fibroblasts secrete ligands that promote a fetal-like state in the intestinal mucosa during early WNT-mediated tumorigenesis. Using a mouse model of WNT-driven oncogenesis and single-cell RNA sequencing (RNA-seq) of mesenchyme cell populations, we revealed a dynamic reprogramming of Pdgfra+ fibroblasts that facilitates WNT-mediated tissue transformation. Functional assays of potential mediators of cell-to-cell communication between these fibroblasts and the oncogenic epithelium revealed that TGFB signaling is notably induced in Pdgfra+ fibroblasts in the presence of oncogenic epithelium, and TGFB was essential to sustain fetal-like growth of organoids ex vivo. Genetic reduction of Cdx2 in the β-catenin mutant epithelium elevated the fetal-like transcriptome and accelerated WNT-dependent onset of oncogenic transformation of the tissue in vivo. These results demonstrate that Pdgfra+ fibroblasts are activated during WNT-driven oncogenesis to promote a fetal-like state in the epithelium that precedes and facilitates formation of tumors.

GSE287339 Dynamic Reprogramming of Stromal Pdgfra-expressing cells during WNT-Mediated Transformation of the Intestinal Epithelium [Figure 3]

Tue, 28 Apr 2026 00:00:00 -0400

GSE287338 Dynamic Reprogramming of Stromal Pdgfra-expressing cells during WNT-Mediated Transformation of the Intestinal Epithelium [Figure 2]

Tue, 28 Apr 2026 00:00:00 -0400

GSE287336 Dynamic Reprogramming of Stromal Pdgfra-expressing cells during WNT-Mediated Transformation of the Intestinal Epithelium [D8]

Tue, 28 Apr 2026 00:00:00 -0400

GSE287335 Dynamic Reprogramming of Stromal Pdgfra-expressing cells during WNT-Mediated Transformation of the Intestinal Epithelium

Tue, 28 Apr 2026 00:00:00 -0400

GSE283429 Changes in Muscularis Macrophage Populations in Diabetes

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Cipriani Gianluca ; Ji Sihan ; Liu Yuanhang ; Farrugia Gianrico ; D'Ambrosio Mario
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Macrophages in the muscle layers of the stomach (Muscularis Macrophages - MMs) play a crucial role in regulating gastric motility and immune homeostasis by interacting with cells in their shared environment and play a central role in development of diabetic gastroparesis, a diabetic complication. The lack of knowledge of the subtypes of murine MMs that reside in the stomach limits a comprehensive understanding of their function and their involvement in disease development.

GSE268995 Molecular Drivers of Neuroinflammation in Amyotrophic Lateral Sclerosis

Tue, 28 Apr 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

GSE264015 Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Melis Akgün Canan ; Corinna Cozzitorto ; Michael Sterr ; Lama Saber ; Eunike S Setyono ; Alessandro Dema ; Kei Kozawa ; Xianming Wang ; Juliane Merl-Pham ; Tobias Greisle ; Ingo Burtscher ; Heiko Lickert
Series Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens

Stem cell-derived glucagon-(α) and insulin-producing (β) cells allow to engineer in vitro biomimetics of islet of Langerhans, the micro-organ controlling glycemia; however, a knowledge gap in the mechanism by which human stem cell-derived α and β cells are specified persists. Mouse studies postulated that Aristaless Related homeobox (Arx) and Paired box 4 (Pax4) transcription factors cross-inhibit each other in endocrine progenitors to promote α/β fate allocation, respectively. To test this model in human, we combined lineage labeling with single-cell multiomic analysis in our newly generated ARXCFP/CFP; PAX4mCherry/mCherry knock-in induced pluripotent stem cell reporter line. Lineage tracing, proteomic and gene regulatory network analysis and potency assays revealed a human specific regulation of α/β cell fate allocation. Pharmacological perturbations previously proposed to trigger α-to-β transdifferentiation or identified by our gene regulatory network led to enhanced endocrine induction and directed α/β cell fate. Studying mechanisms of endocrinogenesis and fate segregation enables to engineer islets in vitro, and has broader implications for cell-replacement therapy, disease modelling and drug screening.

GSE263383 Unbiased niche labeling maps immune-excluded niche in bone metastasis

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Zhan Xu ; Fengshuo Liu ; Xiang Zhang
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

GSE260595 Longitudinal bulk RNA-seq of murine Il10KO colitis

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Jennifer Fransson ; Chiara Sorini ; Eduardo J Villablanca
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

In order to describe in detail the processes involved in chronic colitis, we performed bulk RNA-seq at multiple time points in murine Il10KO colitis. These data were compared to scRNAseq and spatial transcriptomics results from the same mice within the same study. Bulk data were analyzed by identifying differentially expressed genes between time points and treatment groups.

GSE256234 Longitudinal spatial transcriptomics of murine IL10KO colitis

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Jennifer Fransson ; Chiara Sorini ; Eduardo J Villablanca
Series Type : Other
Organism : Mus musculus

In order to describe in detail the processes involved in chronic colitis, we performed spatial transcriptomics at multiple time points in a IL10KO colitis mouse model. These data were compared to bulk RNAseq and scRNAseq (GSE255423) results from the same mice within the same study.

GSE255423 Longitudinal scRNA-seq of murine Il10KO colitis

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Jennifer Fransson ; Chiara Sorini ; Eduardo J Villablanca
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

In order to describe in detail the processes involved in chronic colitis, we performed scRNA-seq at multiple time points in murine Il10KO colitis. These data were compared to bulk RNAseq and spatial transcriptomics results within the same study. scRNAseq data were analyzed by annotating cell clusters and comparing proportions and gene expression programs over time.

GSE251929 Progressive cell fate specification in morphallactic regeneration

Tue, 28 Apr 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing
Organism : Hydra vulgaris

This SuperSeries is composed of the SubSeries listed below.

GSE250594 Single cell analysis of clinically resolved epidermal skin from nickel-challenged individuals treated with either anakinra or placebo

Tue, 28 Apr 2026 00:00:00 -0400

Contributor : Kelvin Yeung
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Background: Topical corticosteroids are used as a standard treatment option in allergic contact dermatitis (ACD). However, the treatment doesn’t inhibit the generation of skin-resident memory T (TRM) cells. These cells play an important role in the pathogenesis of skin flare ups in ACD. Currently, findings in murine models suggest interleukin (IL)-1 inhibition can suppress the immune response to contact allergens. Objectives: To determine if IL-1 inhibition can attenuate acute skin flare-ups and restrict the development of TRM cells. Methods: A murine model was used to investigate the role of IL-1 on epidermal TRM cells by measuring changes in ear thickness and T cell composition. Next, we conducted a randomized, double-blinded, placebo-controlled trial (RCT) [H-22001652; EudraCT number: 2021-004750-39]. Nickel allergic participants were patch-tested at 1) baseline, 2) while being treated with either anakinra or placebo, 3) and 21 days after treatment. The primary outcome was the International Contact Dermatitis Research Group (ICDRG) score 48 hours after patch test application. While secondary outcomes were a reduction of immune cells in clinically cleared and actively inflamed skin. Results: In mice, IL-1 inhibition decreased the number of epidermal CD8+ TRM cells and attenuated skin flare-ups upon re-exposure. Twenty participants were enrolled and completed the RCT, but anakinra failed to improve ICDRG scores. Conclusions: Although IL-1 inhibition has been proven successful in murine models for ACD, there is currently no clinical evidence that suggest it being efficacious as a short-term treatment option for acute skin flare-ups in humans.

GSE245918 Unfolded Protein Response governs an Alternative Splicing program conserved from healthy to malignant cells

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Celine Philippe ; Eleni Maniati ; Kevin Rouaoult-Pierre
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

The unfolded protein response (UPR) is a critical adaptive program triggered upon cellular stresses that profoundly reshapes the transcriptome and translatome. In the very first minutes of cellular stress, translation blockage, RNA decay and RNA granules formation prompt the synthesis of proteins essential to the stress response. Due to the dynamic nature of these processes and ribosome stalling, investigating translation upon stress has proven to be challenging; therefore, our understanding of these mechanisms and translatome rewiring upon stress remains limited. Here, we exploited O-Propargyl-puromycin (OPP) labelling of de novo peptides followed by LC-MS/MS to identify de novo proteins translated upon endoplasmic reticulum stress. Our approach combined to transcriptomic analyses revealed the synthesis of core splicing factor proteins and a profound reshaping of the splicing landscape upon ER stress. We identified a signature of 8 splicing events systematically occurring in eukaryotic cells exposed to ER stress. Using pharmacological, genetic, phosphoproteomic and sequencing approaches, we demonstrated that this specific ERsplice signature is driven by PERK activation and is dependent on splicing factors’ phosphorylation. Our study unveils a new role for ER stress and PERK in splicing regulation, and provide a molecular signature of ER stress through an ERsplice signature conserved from healthy to malignant tissues.

GSE236890 Longitudinal spatial transcriptomics of murine T cell transfer colitis

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Jennifer Fransson ; Chiara Sorini ; Eduardo J Villablanca
Series Type : Other
Organism : Mus musculus

In order to describe in detail the processes involved in chronic colitis, we performed scRNA-seq at multiple time points in a CD45RBhi T cell transfer colitis mouse model. These data were compared to bulk RNAseq and scRNAseq results from the same mice within the same study. Spatial trancriptomics were analyzed by performing NMF to identify spatial patterns of gene expression.

GSE236889 Longitudinal scRNA-seq of murine T cell transfer colitis

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Jennifer Fransson ; Chiara Sorini ; Eduardo J Villablanca
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

In order to describe in detail the processes involved in chronic colitis, we performed scRNA-seq at multiple time points in CD45RBhi T cell transfer colitis mouse models. These data were compared to bulk RNAseq and spatial transcriptomics results from the same mice within the same study. scRNAseq data were analyzed by annotating cell clusters and comparing proportions and gene expression programs over time.

GSE236385 Longitudinal bulk RNA-seq of murine T cell transfer colitis

Tue, 28 Apr 2026 00:00:00 -0400

Contributors : Jennifer Fransson ; Chiara Sorini ; Eduardo J Villablanca
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

In order to describe in detail the processes involved in chronic colitis, we performed bulk RNA-seq at multiple time points in CD45RBhi T cell transfer colitis mouse models. These data were compared to scRNAseq and spatial transcriptomics results from the same mice within the same study. Bulk data were analyzed by identifying differentially expressed genes between time points and treatment groups.