New GEO Series

GSE338478 Periconoid A, a Novel Ergosterol Derivative from Periconia caespitosa, Induces Apoptosis in Nasopharyngeal Carcinoma Cells Accompanied by the Enrichment of Inflammatory Pathways

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Jie Liu ; Jin-Long Huang ; Jing Wang ; Run-Qi Wang ; Tian-Tian Meng ; Jiao-Lin Bao ; Ren-Bo Ding ; Shuai Dong
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Chemical investigation of marine Conus Literatus endophytic fungus Periconia caespitosa HDYXY-1 led to the isolation and characterization of seven novel compounds, including an oxirane-fused cyclohexanone (1), benzothiazole isomers (2 and 3), rare cyano-bearing phenyl ethers (4 and 5), as well as ergosterol derivatives (8 and 9), along with three known analogs (6, 7, and 10). Their structures were elucidated via NMR, HRESIMS, HRAPCIMS, X-ray diffraction, and ECD/DP4+ calculations. Among them, the ergosterol derivative Periconoid A (8) showed potent cytotoxicity against glioblastoma (LN-229, IC50 = 10.05 μM) and nasopharyngeal carcinoma (NPC; CNE2, IC50 = 5.62 μM) cells. Mechanism studies revealed that Periconoid A (8) triggers mitochondria-dependent apoptosis by modulating the Bax/Bcl-2 ratio, activating caspase-3, and inducing PARP-1 cleavage. Transcriptomic analysis indicated that 8 enriches inflammatory response pathways (TNF, JAK-STAT, and NF‑κB), suggesting an inflammation-associated apoptotic mechanism. Molecular docking confirmed a high binding affinity of Periconoid A (8) for the Bcl‑2 protein (–7.6 kcal/mol) through a dual‑polar anchoring network. ADME prediction indicated favorable druggability with high GI absorption and a PAINS‑free profile. Collectively, these findings establish Periconoid A (8) as a promising lead candidate for anti‑NPC drug development, acting through a mechanism that activates inflammation-associated apoptosis.

GSE338234 Effect of VEGF on miRNA profile in miR-1 overexpressing HUVECs for isomiR analysis study

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Asawari Korde ; Giovanni Nigita ; Shervin S Takyar
Series Type : Non-coding RNA profiling by high throughput sequencing
Organism : Homo sapiens

MiRNAs are generated through a finely tuned multi-step process that includes precise cropping and cleavage of their precursors. The mature miRNA is then loaded onto an argonaute (Ago) protein to form an RNA-induced silencing complex (RISC) and target messenger RNAs. Most of the mechanisms of miRNA regulation target one of the steps in the biogenesis. However, through analysis of miR-1 precursors, we demonstrate that VEGF stimulation induces degradation (decay) of mature miR-1-3p without affecting its precursors. This analysis also identified a specific miRNA 3’-adenylation pathway that targets the guide strand after RISC loading. In this study we detected miRNA sequences which are modified at their 3' end.

GSE338219 吡咯喹啉醌改善了自然衰老小鼠与增强线粒体生物能量相关的认知相关行为表现

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : 云燕 ; 迪鄧 ; 春霞棕褐色
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

We investigated whether pyrroloquinoline quinone (PQQ) could improve cognitive performance in twenty-month-old naturally aged mice and explored the potential mechanisms involved. Results showed that PQQ supplementation improved spatial working memory and recognition memory without inducing anxiety-like behavior, and was associated with better preservation of hippocampal neuronal integrity. In HT-22 hippocampal neuronal cells, PQQ reduced reactive oxygen species (ROS) accumulation, restored mitochondrial membrane potential, and enhanced mitochondrial respiratory capacity. Hippocampal transcriptomic analysis and upstream regulator prediction identified SIRT1 as a major regulator associated with the PQQ-induced transcriptional response, while uncoupling protein 2 (UCP2) emerged as a candidate downstream mitochondrial effector. Consistently, PQQ increased hippocampal SIRT1 protein expression and downregulated UCP2 at both mRNA and protein levels. Pharmacological inhibition of SIRT1 attenuated the PQQ-induced increase in ATP production and partially weakened the regulatory effect of PQQ on UCP2, supporting the involvement of SIRT1 in PQQ-associated mitochondrial bioenergetic regulation. Collectively, these findings indicate that PQQ improves cognitive-related behavioral performance in naturally aged mice and is associated with mitochondrial bioenergetic regulation, and suggest that modulation of a SIRT1–UCP2-associated pathway may contribute to its neuroprotective effects.

GSE338200 Cannabidiol reverses microglial exhaustion in aged Gulf War Illness mice

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Kwang-Mook Jung ; Hye-Lim Lee ; Daniele Piomelli
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Gulf War Illness (GWI) affects up to one-third of 1990–1991 Gulf War veterans and is associated with chronic low-grade neuroinflammation, yet its cellular substrates remain unclear and targeted pharmacological therapies are still limited. By using bulk RNA-seq analyses of FACS-purified microglia in an established GWI mouse model, we uncovered a multi-lineage primed neuroimmune signature in aged GWI mice. Systemic lipopolysaccharide (LPS) elicited an amplified pro-inflammatory response in the brains of GWI mice compared to age-matched controls, yet paradoxically, microglia were transcriptionally hyporesponsive to LPS, with inverted antigen presentation module score indicative of a microglial exhaustion phenotype. Chronic cannabidiol (CBD) attenuated neuroimmune priming at baseline, reshaping microglial translational and energetic states. Under immune-stimulated conditions, CBD partially restored GWI-associated deficits in microglial antigen presentation and oxidative phosphorylation, defining a therapeutic axis amenable to pharmacological intervention.

GSE338199 Cannabidiol reverses neuroimmune priming in aged Gulf War Illness mice

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Kwang-Mook Jung ; Hye-Lim Lee ; Daniele Piomelli
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

GSE338197 Dissection of Poly(A)-binding protein (PABPC) cellular function using degron-mediated depletion with replacement

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Ryan Y Muller ; Kiara X Wang ; David P Bartel
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Cytoplasmic poly(A)-binding proteins (PABPCs) are essential and highly abundant regulators of mRNA stability and translation, but their cellular functions have been difficult to dissect due to slow turnover and the lethality observed upon loss of both major paralogs, PABPC1 and PABPC4. To enable structure–function analysis of PABPC in human cells, we developed a protein-replacement platform that couples rapid auxin-inducible degradation of endogenous PABPC1 and PABPC4 with doxycycline-controlled expression of engineered PABPC variants. This approach enables acute removal of native PABPC and real-time assessment of how specific domains, paralogs, and sequence alterations support cellular fitness, shape transcriptome profiles, and regulate poly(A)-tail length. Using this system, we show that the RRM4 domain of PABPC1 is essential for growth, whereas post-translationally modified lysines within RRM4 are individually dispensable. Paralogs and variants with heterologous RRM4 domains vary in their ability to substitute for PABPC1, revealing functional divergence among PABPCs. Transcriptome profiling identifies variant-specific regulatory signatures, and dose-controlled rescue further delineates the relationship between PABPC variant abundance and global poly(A) tail lengths in vivo. Together, this platform provides a generalizable strategy for dissecting PABPC biology in the cellular context using rationally designed variants.

GSE338196 Neuroimmune priming and microglial exhaustion in aged Gulf War Illness mice

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Kwang-Mook Jung ; Hye-Lim Lee ; Daniele Piomelli
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

GSE338180 Cell senescence emerges as a hallmark and therapeutic target of chronic intracellular infection

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Edoardo Scarpa ; Doriana Oliveri ; Diego Rondelli ; Carla Chernichero ; Federico Russo ; Riccardo Nodari ; Giorgia Moschetti ; Anna Griego ; Marta Zaccaria ; Federico Di Marco ; Fabio Saliu ; Gabriele Marchello ; Ferdinando Cannella ; Manuel Albanese ; Gianluca Cidonio ; Lara Manganaro ; Daniela M. Cirillo ; Raffaele De Francesco ; Sergio Abrignani ; Raffaella Di Micco ; Nicola I. Lorè ; Loris Rizzello
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Intracellular pathogens are ideal candidates for modelling the pathophysiology of chronic infection, as they hide within host cells and avoid immune clearance by reshaping cellular fate. This study unveils how the intracellular pathogen Mycobacterium abscessus (Mab) reprograms alveolar macrophages towards a senescent state -a multifaced phenotype marked by proliferative arrest, distinctive morphological shifts, activation of DNA damage signalling cascade, and secretion of senescence-associated secretory phenotype (SASP) factors. Mab-induced DNA damage emerged as the primary driver of senescence, while SASP secretion acts as a molecular broadcaster, propagating secondary senescence in neighbouring, uninfected cells through paracrine signalling. This cascading wave of amplified senescence underscores a detrimental effect on the tissue microenvironment, turning it into a chronic inflammatory niche that facilitates Mab persistence and immune evasion. By leveraging evidence of chronic infection-induced senescence, we prototyped a therapeutic approach where senolytic drugs selectively eradicated senescent cells and significantly reduced bacterial burden, similarly to antibiotics.

GSE338160 Rapid and functional intestinal regeneration after full-organ transection in zebrafish larvae is regulated by opposing effects of IL-22 and IL-26

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Medina-Yáñez Ignacio ; Hernandez Pedro
Series Type : Expression profiling by high throughput sequencing
Organism : Danio rerio

The intestinal epithelium is among the most regenerative tissues, continuously renewing and repairing after damage. Severe injuries that disrupt all tissue layers, however, pose a distinct challenge, requiring restoration of the epithelium together with its surrounding tissues. Whether and how a vertebrate intestine can restore architecture and function after complete loss of gut continuity remains unknown. Here, we establish a larval zebrafish model of severe intestinal injury, in which full-organ transection disrupts all gut tissue layers. Following injury, the intestine rapidly reattaches, restores lumen continuity, and resumes food transit. This repair process is accompanied by mesenchymal remodeling and restoration of muscle continuity, and is promoted by transient epithelial proliferation. Injury induces a sox17-expressing epithelial progenitor-like state, with localized re-expression of this embryonic gut marker at the wound site. Injury also triggers transient neutrophil and macrophage recruitment to the wound site and broadens the range of epithelial cell types that express il22. STAT3 signaling is required for timely epithelial reattachment and injury-induced proliferation. Loss of IL-22 blunts early repair-associated responses, impairs reattachment, reduces proliferation, and limits lumen restoration. In contrast, loss of IL-26 enhances early epithelial repair programs, accelerates gap closure, and elevates proliferation in a mitosis-dependent manner. Together, these findings establish zebrafish larvae as a tractable vertebrate model for full-organ intestinal regeneration and identify IL-22 and IL-26 as opposing regulators of STAT3-associated repair

GSE338134 A Lactic Acid-Chac1 Axis Regulates Ferroptosis-Associated Cell Death and Tumor Progression

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Lilan He ; Aaron Q Zhang ; Rui Wu ; Shitong Zhong ; Jiali Chen ; Bin Shao ; Siyu He ; Jingyuan Lu ; Fan Hu ; Jiayun Yu ; Hanwen Li
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Tumor metabolic reprogramming plays a critical role in cancer progression, yet the direct involvement of lactic acid in regulating tumor cell death remains incompletely understood. In this study, we identified lactic acid as a previously underappreciated regulator of tumor cell fate and investigated whether lactic acid induces ferroptosis-associated cell death in tumor cells. Lactic acid suppressed tumor cell viability in a dose-dependent manner across multiple tumor cell lines and triggered cell death with both apoptotic and non-apoptotic features. Transcriptomic analysis revealed significant enrichment of ferroptosis-related pathways, accompanied by glutathione depletion, Gpx4 downregulation, and increased oxidative stress. Pharmacological inhibition using Ferrostatin-1 and genetic modulation of Slc7a11 supported the involvement of ferroptosis in lactic acid-induced cytotoxicity. Mechanistically, we identified Chac1 as an important mediator linking lactic acid-induced metabolic stress to ferroptosis-associated tumor cell death, as Chac1 knockdown attenuated cytotoxicity in vitro while promoting tumor growth and metastasis in vivo. Furthermore, Chac1 deficiency was associated with enhanced metastatic progression, suggesting that suppression of ferroptosis may facilitate tumor progression, at least in part, potentially associated with alterations in tumor immune cell infiltration. Collectively, these findings uncover a previously unrecognized link between lactic acid and ferroptosis, establish Chac1 as a critical regulatory node, and highlight the therapeutic potential of targeting the lactic acid-Chac1-ferroptosis axis in cancer treatment.

GSE338129 HP1α depletion and TGFβ activation exert antagonistic effects on 3D genome organization.

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Fabiana Patalano ; Oda Hovet ; Roberto Rossini ; Maxim Nekrasov ; Yasmin Dijkwel ; Bhumika Azad ; Tatiana Soboleva ; Rein Aasland ; David Tremethick ; Jonas Paulsen
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens

The three-dimensional (3D) organization of the human genome plays a critical role in regulating gene expression and is frequently disrupted in cancer. However, how key factors like Heterochromatin Protein 1 alpha (HP1α) and Transforming Growth Factor beta (TGFβ) remodel this architecture to drive tumorigenesis remains poorly understood. We investigated the effects of HP1α knockdown and TGFβ treatment on higher-order chromatin structure and gene expression in human mammary epithelial cells. Our findings reveal that HP1α depletion and TGFβ stimulation exert distinct and opposing effects on genome compartmentalization and subcompartmentalization. HP1α knockdown drives a genome-wide shift of chromatin from transcriptionally inactive B compartments to active A compartments. This is accompanied by a stepwise redistribution of A subcompartments toward the most transcriptionally active state (A3), and the upregulation of oncogenic genes involved in EMT and proliferation. In contrast, TGFβ treatment promotes chromatin compaction, increases the proportion of B compartments, and drives a stepwise reduction in active A subcompartments. Our results highlight the differential roles of HP1α and TGFβ in shaping the 3D genome and underscore how precise, stepwise architectural changes contribute to malignant transformation. This study provides critical insight into how chromatin architecture acts as a regulatory layer in breast cancer development.

GSE338111 Sex-specific differences of amlexanox in a mouse model for atherosclerosis and MASLD

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Eleonora Mungo ; Tobias Schmid ; Silvia Kuntschar ; Sofie P Meyer ; Ellen Niederberger
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Inhibitor‑κB kinase epsilon (IKKε) is a non‑canonical IκB kinase involved in NF‑κB signaling and type I interferon responses. We recently demonstrated sex‑dependent effects of IKKε deletion on atherosclerosis and metabolic dysfunction‑associated steatotic liver disease (MASLD), with male knockout mice showing protection against both diseases, while female mice exhibited exacerbated inflammatory and metabolic disturbances. These divergent outcomes were linked to differential effects on inflammatory pathways and lipid metabolism. To evaluate the therapeutic potential of pharmacological IKKε inhibition, we treated wild type mice with established atherosclerotic plaques and hepatic steatosis - induced by PCSK9 gain‑of‑function and Paigen diet - with the IKKε inhibitor amlexanox. Amlexanox modulated serum lipid levels and altered plaque composition but did not halt plaque progression. In the liver, treatment produced marked sex‑specific effects: male mice exhibited substantial improvement in steatosis, whereas female mice showed worsened lipid accumulation. These outcomes were reflected in pronounced sex‑dependent differences in serum and hepatic lipid and metabolite profiles, indicating regulation of fatty acid and bile-acid metabolism predominantly in males. Protein analyses in liver and adipose tissue further supported opposing metabolic and inflammatory responses between sexes after amlexanox treatment. Collectively, our findings indicate that therapeutic IKKε inhibition with amlexanox does not prevent progression of advanced atherosclerosis in this model but effectively ameliorates MASLD in male mice. In contrast, female mice experience aggravated hepatic lipid deposition. These results underscore the importance of incorporating sex‑specific analyses in metabolic and cardiovascular research and highlight the need to evaluate therapeutic strategies such as amlexanox in both sexes.

GSE338107 Innate immune activation profiles are associated with polarization of the T cell response to recombinant arenaviral vectors

Tue, 14 Jul 2026 00:00:00 -0400

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

Arenavirus-based vectors are uniquely positioned to generate durable T cell responses against tumors, which remains a central challenge in cancer immunotherapy. Two members of the arenavirus family, Lymphocytic choriomeningitis virus and Pichinde virus, were genetically engineered to encode a non-oncogenic fusion protein, originating from human papillomavirus 16 E6 and E7. Hereafter, these vectors are referred to as HB-201 and HB-202, respectively. HB-201 alone or in combination with HB-202 elicited strong and durable E6/E7-specific CD8+ T cell responses in HPV 16+ cancer patients . Despite their classification within the same virus family, Lymphocytic choriomeningitis virus and Pichinde virus are phylogenetically distant, which may influence virus-host interactions and the pathways leading to antiviral immune responses. Previous studies showed that both vectors infect and activate professional antigen presenting cells. To elaborate on these findings, this study aimed to characterize in depth the innate immune response to HB-201 and HB-202 by single cell sequencing in an in vitro human PBMCs infection model. We confirmed the preferential infection of antigen presenting cells for both vectors, with HB-201 infecting the cross-priming conventional dendritic cell subset cDC1 more efficiently than HB-202. Furthermore, HB-201 induced stronger type I interferon responses than HB-202, as well as quantitative and qualitative differences in inflammatory response linked to a distinct reshaping of monocyte subsets towards intermediate and non-classical monocytes. Antigen presentation and T cell priming cytokines in dendritic cells appeared to favor antiviral CD8+ T cell responses upon HB-201 infection, whereas a more balanced CD4+ and CD8+ priming profile was observed upon HB-202 infection. Immunogenicity data from patients treated with HB-201 and HB-202 confirmed the in vitro findings with functional differences in early T cell response. Thus, despite their shared origins within the arenavirus family, HB-201 and HB-202 demonstrate distinct differences in early host-virus interaction, potentially resulting in shaping unique T cell responses.

GSE338097 RNA-seq analysis on maize plants treated with Streptomyces sclerogranulatus

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Yuanlin Qi ; Jinai Yao
Series Type : Expression profiling by high throughput sequencing
Organism : Zea mays

In this studies, we sought to isolate and identify a novel Streptomyces sclerogranulatus SM3-7 strain with biocontrol potential and to elucidate the antibacterial secondary metabolites responsible for its antagonistic activity.

GSE338066 Isolation and Characterization of a Novel Streptomyces murinus Strain with Dual Activities: Biocontrol of Maize Foliar Pathogens and Growth Promotion

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Yuanlin Qi ; Jinai Yao
Series Type : Expression profiling by high throughput sequencing
Organism : Zea mays

This study evaluated the biocontrol efficacy, growth-promoting potential, and molecular mechanisms of the actinomycete strain FJSM-07, identified via 16S rDNA sequencing as Streptomyces murinus.

GSE337765 Transcriptomic analysis of unwounded skin, vehicle-treated wounds, and brequinar-treated wounds in mice

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Ken Araki ; Akihiko Uchiyama ; Yoko Yokoyama ; Yohei Morishita
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Bulk RNA sequencing was performed to investigate transcriptomic changes in unwounded skin, vehicle-treated wounds, and brequinar-treated wounds collected from mice on day 9 after wounding. The study aimed to identify molecular pathways associated with the brequinar-induced pyoderma gangrenosum-like phenotype and to compare gene expression profiles among experimental groups.

GSE337706 Exploring Platelet-Covered and Naked Circulating Tumor Cells: A Single-Cell Transcriptomic Perspective [scRNA-seq Singleron]

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Michal Sieczczynski ; Krzysztof Pastuszak ; Marcin Banacki ; Kamil Langowski ; Sylwia Lapinska-Szumczyk ; Anna Samelak-Czajka ; Paulina Jackowiak ; Iwona Inkielewicz-Stepniak ; Anna Supernat ; Anna Joanna Zaczek
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Circulating tumor cells (CTCs) and platelets can be collected simultaneously during liquid biopsy; however, their interaction in the form of platelet-covered CTCs (pcCTCs) remains only partially understood. This submission contains single-cell RNA sequencing data generated from PBMC/buffy coat fractions from 29 donors: 12 patients with high-grade serous ovarian carcinoma, 4 non-malignant gynecological controls, 10 patients with breast cancer, and 3 healthy donor controls. The dataset was used to detect and characterize candidate naked CTCs and pcCTCs and to compare their transcriptomic profiles with platelet and cancer-related signatures.

GSE337705 Exploring Platelet-Covered and Naked Circulating Tumor Cells: A Single-Cell Transcriptomic Perspective [scRNA-seq 10x_Poznan]

Tue, 14 Jul 2026 00:00:00 -0400

GSE337702 Mechanical stiffness-promoted tumor tagging to navigate radiopharmaceuticals: Single-cell RNA sequencing revealed the fate of MSC after tumor homing

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Xiujie Yang ; Chunhong Zheng ; Zhaofei Liu
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Radiopharmaceutical imaging and targeted radionuclide therapy rely on endogenous molecular targets which are frequently heterogeneous, absent, or lost during cancer progression. We developed SMART, a Stiffness-responsive Mesenchymal stem cell (MSC)-Assisted Relayed tumor-Targeting platform that converts elevated matrix stiffness, a conserved biophysical feature of tumors, into localized expression of synthetic radiopharmaceutical targets. Engineered MSCs sensing stiff tumor microenvironments induced tumor-restricted expression of prostate-specific membrane antigen (PSMA), enabling 68Ga-PSMA-617 positron emission tomography (PET) imaging and 177Lu-AB-PSMA-617 therapy across diverse tumor models. SMART-enabled PET improved detection sensitivity relative to 18F-fluorodeoxyglucose PET, including in brain, lung, and bone metastases. The platform is modular, extendable to targets such as somatostatin receptor 2, and compatible with induced pluripotent stem cell (iPSC)-derived MSCs. SMART therefore decouples radiotheranostic performance from endogenous biomarker status and establishes a generalizable strategy for targeting biophysical hallmarks of cancer.

GSE337675 Truncating ASXL1 variants rewire cellular metabolism via mitochondrial pyruvate carrier repression

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Isabella Lin ; Michael Reyes ; Valerie Arboleda
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Bohring-Opitz syndrome (BOS, OMIM#605309) is a rare neurodevelopmental disorder caused by heterozygous and truncating variants in ASXL1 (Additional Sex Combs Like 1), a chromatin-associated epigenetic regulator that forms the catalytic PR-DUB complex with BAP1. Truncating ASXL1 variants are also recurrent somatic drivers in myeloid leukemia, yet the metabolic consequences of these mutations remain undefined. Using patient derived dermal fibroblasts, we show that truncating ASXL1 variants drive a Warburg-like metabolic state characterized by increased glycolytic flux, and accumulation of pyruvate and lactate. Stable isotope tracing revealed preservation of glucose-derived carbon incorporation into tricarboxylic acid (TCA) cycle intermediates, suggesting compensatory metabolic adaptation to maintain pyruvate-dependent TCA cycle metabolism. Overexpression of truncating ASXL1 constructs in cell models replicated this phenotype. Mechanistically, truncated ASXL1 shows decreased occupancy at an H3K4me3-marked enhancer upstream of mitochondrial pyruvate carrier 2 (MPC2), together with BAP1 co-recruitment, and selectively reduces MPC1 and MPC2 protein levels through a mechanism that is independent of transcript levels. Pharmacologic inhibition of the MPC reproduces both the metabolic and Wnt signaling phenotypes of BOS cells, while canonical Wnt activation also increases glycolytic flux but without reducing the MPC abundance, implicating that reduced MPC abundance acts upstream of signaling dysregulation. These findings define a previously unrecognized pathway connecting gain-of-function ASXL1 truncation to chromatin-level regulation of mitochondrial pyruvate transport, and identify the MPC as a central mediator of epigenetic-metabolic crosstalk in both a rare developmental syndrome and ASXL1-mutated myeloid malignancies.

GSE336414 Repeated mild spinal cord contusions exacerbate tauopathy development in PS19 mice

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Nicolas Halloin ; Nicolas Debortoli ; Hélène Collignon ; Zoé Marlier ; Kunie Ando ; Valérie Suain ; Louise Conrard ; Margaux Mignolet ; Lindsay Sprimont ; Marino Caruso ; Aurélie Ladang ; Jonathan Degosserie ; Karelle Leroy ; Charles Nicaise
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus ; blank sample

Growing evidence indicates that traumatic brain injury constitutes a significant risk factor for the development of age-related tauopathies, yet the consequences of repeated mild spinal cord injuries (rmSCI) remain insufficiently explored. In this context, we developed a mouse model undergoing two successive mild cervical contusions during young adulthood, which do not produce immediate functional motor deficits, thereby mimicking real-life conditions of occupational- or sports-related trauma. rmSCI were induced in PS19 (hTauP301S) mice developing late-onset tauopathy in the brain and in the spinal cord. The consequences of rmSCI were assessed on motor outcomes and tauopathy signature in injured PS19 mice during ageing. rmSCI exacerbated age-dependent motor deficits and significantly increased tau hyperphosphorylation on the pSer422 and pSer202/Thr205 epitopes. Pathological changes, initially confined to the epicenter of the contusions, extended along a caudo-rostral axis reaching the thalamus. While rmSCI did not modify intraspinal tau aggregation, spinal cord-derived protein extracts displayed enhanced seeding activity in vitro. Although causality was not established with tau hyperphosphorylation status, early response towards mild spinal contusions included glial activation and upregulation of interferon-stimulated genes. Together, these data identify rmSCI as a previously underappreciated modifier of tau pathology and disease progression. Moreover, this study provides a novel experimental link between mild central nervous system injuries and exacerbation of tauopathy and suggests the involvement of type I interferon signalling or sustained glial activation. Ultimately, these findings underscore the importance of preventing even mild spinal injuries in individuals at risk of tauopathy.

GSE330051 In vivo DNA damage protection during cell migration across confining embryonic tissue environments

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Zainalabdeen Alhashem ; Mint R Htun ; You-Hsuan Liu ; Hanna-Maria Hakkinen ; Elena Scarpa
Series Type : Expression profiling by high throughput sequencing
Organism : Danio rerio

In physiology and in disease, cells often migrate through narrow spaces, such as leukocytes undergoing diapedesis or cancer cells during dissemination. Cultured cells under physical confinement can experience mechanical stress due to deformation of the nucleus. Nuclear deformation leads to loss of nuclear integrity and DNA damage, and it has been proposed to underlie cancer initiation and progression. In vivo, the consequences of physical confinement on physiological cell migration remain poorly understood. Here, we use the zebrafish neural crest as an in vivo model to address how multipotent embryonic cells respond to physical confinement during developmental migration. By measuring the size of extracellular spaces, we found that the level of tissue scale confinement increases from head to tail along the embryonic antero-posterior axis. Nuclear morphometrics analysis shows that neural crest experience dramatic nuclear deformation during their migration between adjacent tissues, which quantitatively scales with tissue confinement. By using complementary genetic and mechanical strategies to ablate the surrounding tissue, we observe a rescue of nuclear deformation in vivo. Surprisingly, we found that while deformation of the neural crest nucleus causes nucleo-cytoplasmic leakage, it does not cause nuclear envelope rupture or increase DNA damage even upon extreme deformations. Instead, confined migratory neural crest show decreased LaminB2 at the nuclear envelope. By perturbing LaminB2 expression levels, we discover that loss of LaminB2 facilitates fast recovery from deformation, while sustained expression of LaminB2 results in persistently deformed nuclei, highlighting a role for LaminB2 in nuclear shape deformability. Using a photoconversion and RNA-seq approach, we uncover upregulation of a large network of DNA repair genes in confined trunk neural crest, suggesting these stem cells might be resistant to confinement-induced mechanical stresses. In summary, we establish the neural crest as a physiological framework, uncovering dynamic adaptations to tissue confinement in vivo.

GSE327865 Upf3a-dependent genetic compensation sustains BMP robustness during murine odontogenesis

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Chensheng Lin ; Xi Zheng ; Lanting Zhang ; Ying Chen ; Shunting Chen ; Yihang Xiang ; Huan Huang ; Yanding Zhang ; Xuefeng Hu
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

Homology-dependent genetic compensation response (HDGCR), also known as transcriptional adaptation (TA), represent evolutionarily conserved mechanisms that buffer deleterious mutations through transcriptional upregulation of functionally related genes. However, direct in vivo evidence for HDGCR in mammal species remains limited. Bone morphogenetic protein (BMP) signaling is indispensable for murine tooth development, yet extensive ligand redundancy frequently masks phenotypes in single-gene knockouts, making odontogenesis an ideal organ system to interrogate HDGCR. Here, we generated a conditional Upf3a knockout mouse (Upf3af/f), exhibiting normal survival and tooth development when crossed with Wnt1-Cre mice, for in vivo HDGCR studies. Loss of Upf3a abolished the compensatory upregulation of paralogous Bmp4 following Bmp2 deletion, functionally mimicking a Bmp2/Bmp4 double-deficient state. This disruption promoted proliferation of dental pulp cells and root progenitor cells and inhibited differentiation of odontoblasts, leading to severe defects in dentinogenesis and root development. ChIP-seq revealed that this organ-specific, Upf3a-dependent HDGCR operates independently of H3K4me3 enrichment at the Bmp4 promoter. Collectively, these findings provide in vivo mammalian evidence that Upf3a-dependent HDGCR critically modulates BMP signaling robustness during murine odontogenesis within a defined developmental and tissue context.

GSE327278 Analysis of transcriptional changes associated with acquired resistance to docetaxel in HR+/HER2- breast cancer cell line MCF-7

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Cyril Corbet ; Martin Michaelis ; Jindrich Cinatl Jr ; Jérôme Ambroise
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Resistance to neoadjuvant chemotherapy in HR+/HER2- breast cancers is increasingly recognized as a consequence of tumor cell plasticity rather than fixed genetic alterations. Large-scale genomic analyses comparing tumors before and after chemotherapy have failed to identify recurrent mutations that consistently account for treatment failure. Instead, resistance is thought to arise predominantly through non-genetic, adaptive mechanisms, including the acquisition of gene expression changes that allow cancer cells to survive chemotherapy-induced stress and later re-enter proliferative programs.To uncover transcriptional adaptations to docetaxel, a chemotherapeutic agent used in the NAC clinical setting, we performed bulk RNA-sequencing on parental and docetaxel-resistant MCF-7 cells.

GSE322528 Genetic engineering of carbon monoxide dehydrogenases produces distinct autotrophic phenotypes in Clostridium autoethanogenum

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Kurshedaktar M Shaikh ; Kristina Reinmets ; Pratik R Pawar ; Clara V Carneiro ; Kaspar Valgepea
Series Type : Expression profiling by high throughput sequencing
Organism : Clostridium autoethanogenum

Acetogens are promising microbes for sustainable biomanufacturing but improving acetogen gas fermentation requires efficient conversion of CO and CO2 into fuels and chemicals. Carbon monoxide dehydrogenase (CODH) enzymes couple carbon fixation to energy conservation in acetogens and serve as potential regulatory modules for tuning autotrophic metabolism. Intriguingly, the model-acetogen Clostridium autoethanogenum lost its unique truncation in the bifunctional CODH (acsA), essential for autotrophy, during autotrophic adaptive laboratory evolution while obtaining superior phenotypes. Additionally, protein expression of the monofunctional CODH cooS1 is high and conditionally-regulated in C. autoethanogenum. Here, we genetically engineered CODHs in C. autoethanogenum by replacing the stop codon in acsA with leucine (strain Leu_SNP) or serine (Ser_SNP), and deleting cooS1 (ΔcooS1). Phenotyping in autotrophic batch and chemostat cultures revealed altered growth profiles and significant redistribution of carbon and redox flows in SNP strains, whereas ΔcooS1 showed moderate and condition-dependent effects. Surprisingly, structural modelling identified no conformational differences between wild-type and mutant AcsA proteins. While transcriptomics showed limited transcriptional changes in ΔcooS1, it suggested potential transcriptional adjustments linked to reduced robustness and altered product profile of Leu_SNP. Our results demonstrate the impact of CODHs on autotrophy and offer targets for rational engineering of acetogen cell factories.

GSE318316 HERC4-mediated ubiquitination licenses RIPK1 to initiate TNF-induced cell death

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Haohao Lu ; Tongde Du ; Sudan He
Series Type : Other
Organism : Homo sapiens

TNF can activate both pro-survival and pro-death signaling downstream of tumour necrosis factor TNFR1. Survival signaling originates from TNFR1-containing membrane-bound Complex I, while death signaling is driven by cytosolic Complex II. RIPK1 is a central component of both complexes, but the molecular switch converting RIPK1 from a pro-survival scaffold in Complex I to a pro-death kinase in Complex II has remained elusive.Here, we identify the E3 ligase HERC4 as the molecular determinant of pro-survival or pro-death signalling. We show that HERC4 binds Complex-I-derived S166-phosphorylated, kinase-active RIPK1 and ubiquitinates it within its death domain. This enables RIPK1 oligomerization and assembly of the apoptosis-inducing RIPK1–FADD–caspase-8-containing Complex IIa and, upon caspase inhibition, formation of the necroptosis-initiating RIPK1–RIPK3-containing necrosome. HERC4 deficiency protects mice from TNF-induced systemic inflammatory response syndrome and acute liver injury. We show that HERC4 is the link enabling Complex I-derived kinase-active RIPK1 to initiate death signaling.

GSE302966 Comparative phenotypic characterisation of mutant human bronchial epithelial cells in vitro and in vivo

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Carlos Lopez-Garcia ; Robert Sellers
Series Type : Other
Organism : Homo sapiens

Development of tractable and robust models of cancer depends on a transparent, detailed and critical evaluation of their advantages and disadvantages for their use in basic and translational cancer research. Specifically, identifying the phenotypic differences of cancer cells in vivo and in vitro is essential to select the most informative experimental setting without compromising the scalability, versatility and cost-effectiveness of research projects. Development of tractable and robust models of cancer depends on a transparent, detailed and critical evaluation of their advantages and disadvantages for their use in basic and translational cancer research. Specifically, identifying the phenotypic differences of cancer cells in vivo and in vitro is essential to select the most informative experimental setting without compromising the scalability, versatility and cost-effectiveness of research projects. Our observations showed similar results in vivo and in vitro regarding the essential components for the transformation of hBECs. We also observe differences in gene expression that suggest an increase in motility in vivo and, importantly, an alternative mechanism of LUSC development that depends on squamous differentiation mediated by epithelial inactivation of NOTCH1.

GSE292334 The tumor suppressor SMAD4 is a gatekeeper for genome stability

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Atmika Paul ; Holger Bastians ; Maren Sitte ; Gabriela Salinas
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Cancer chromosomal instability (CIN) causes structural and numerical chromosome aberrations and acts as a driver for tumor progression and poor patient outcome. However, the mechanisms driving CIN are incompletely understood. In this study, we identified SMAD4, a key tumor suppressor in colorectal and pancreatic cancers, as a gatekeeper for genome stability. Loss of SMAD4 results in homologous recombination DNA repair defects, DNA replication stress and mitotic errors, resulting in genome instability. SMAD4 acts as part of BMP signaling and ensures genome stability through its transcriptional target inhibitor of DNA binding 3 (ID3). Consequently, abrogation of BMP signaling or ID3 phenocopies the genome maintenance defects induced upon loss of SMAD4. Thus, our study defines SMAD4 as a key suppressor of genome instability in human cancer.

GSE292182 Direct interaction of Vδ7 TCRs with IL17RA drives the differentiation of TH1-like γδT cells

Tue, 14 Jul 2026 00:00:00 -0400

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

Of the three classes of lymphocytes that constitute the adaptive immune system, γδT cells are the only class for which the principles of antigen recognition remain enigmatic. While endogenous γδTCR ligands are thought to regulate γδT cell development, their identities are largely elusive. Here, we identified the cytokine receptor chain IL17RA as a γδTCR ligand that drove the differentiation of Vδ7+ γδT cells with a TH1-like effector program. IL17RA promoted this differentiation through an interaction involving germline-encoded regions of the Vδ7 chain, enabling the selection of cells with a diverse CDR3 repertoire – therefore acting as a non-clonotypic γδTCR ligand. Together with the non-clonotypic mode of γδTCR engagement by butyrophilins, these results suggest that such interactions represent a general biological mechanism shaping the γδT cell compartment.

GSE272274 Effects of hepatic mARC1 inhibition in a mouse model of liver fibrosis

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Erin S Coyne ; Yang Liu ; Brendan Gongol ; Stacey Meyers ; Wendy Blumenschein ; Saswata Talukdar
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Metabolic-dysfunction associated steatohepatitis (MASH) is defined by increased liver adiposity that is causative to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Despite the high prevalence of the disease, there are currently few treatment options in part because the mechanistic basis causative to hepatic fatty acid biogenesis and accumulation are unresolved. Recent evidence indicates that enhanced mitochondrial amidoxime-reducing component 1 (mARC1) induction is associated with increased hepatic triglyceride accumulation and reduced plasma triglycerides indicting that it may play an important role in NASH pathogenesis. The goal of this study is to explore the therapeutic potential of mARC1 inhibition on the inhibition or reversal of NASH pathogenesis in a mouse model of diet induced MASH.

GSE271062 Comparative transcriptomics of Nipah virus infection in human and fruit bat cells

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Claudia Gonzalez ; Carine Rey ; Omran Allatif ; Severine Croze ; Olivier Reynard ; Branka Horvat
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens ; Pteropus vampyrus

We used bulk RNA sequencing to investigate the transcriptomic signature of fruit bat and human cells after Nipah virus infection. We have infected immortalized and bat and human cells and collected samples at 0, 8, 24, 48 hours-post-infection (hpi). Positive cells to infection were sorted at 24 and 48hpi. We also have infected primary bat and human cells and collected samples at 0 and 48hpi. We analyzed inter- and intra-species responses to highlight mecanims allowing bat to control Nipah virus infection.

GSE254260 Single cell RNA-sequencing of H9 human embryonic stem cell-derived cortical organoid slice cultures (ALI-COs) at various timepoints

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Lea D Wenger ; George M Gibbons ; Kornelia Szebenyi ; Andras Lakatos
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

scRNA-seq analysis of 100, 150, 290, 360 and 390 day old human cortical organoids grown at the air-liquid interface (ALI-COs). Investigations reveal a gliogenic switch, resulting in two distinct astrocyte populations with different propensities for synapse regulation.

GSE253492 Transcriptional Regulation by NFATc1 and NFATc2 in chronically activated CD8+ T cells

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Stefan Klein-Hessling ; Salvador Sampere Birlanga ; Edgar Serfling ; Thorsten Bischler
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Both chronic viral infections and progressing tumors result in dysfunctional CD8+T cells in a process called exhaustion. Such TEX cells exhibit a reduced proliferative capacity, reduced cytokine expression and target cell killing. They are characterized by increased expression of co-inhibitory receptors as PD-1, Tim-3, Lag-3 and TIGIT, and resistance against immune checkpoint therapies (ICT). These cells develop from so called precursors of exhaustion (TPEX) that express high levels of TCF1 and Ly108 and still respond to ICT. The NFAT factors NFATc1 and NFATc2 play a crucial role in exhaustion of CD8+ T cells and, thereby, in suppression of tumor formation by immune cells. NFATc1 is the most prominent NFAT factor in nuclei of activated T cells and the inducible isoform NFATc1/aA, is strongly expressed in chronically induced CD8+ T cells. The inducible expression of NFATc1/aA is controlled by the distal enhancer E2 and conditional ablation of E2 abolish this induction. We compared here the transcriptome of in vitro chronically stimulated CD8+ T cells with different NFAT deficiencies. While the ablation of NFATc2 resulted in reduced expression of exhaustion markers Tim3 and Tigit and increased expression of Tcf7 and Slamf6, only minor effects on exhaustion markers were detected upon ablation of inducible NFAT1/aA or entire NFATc1.

GSE231695 Widespread transmission of DNA supercoiling and selective topoisomerase utilization regulates torsional stress within the neuronal genome

Tue, 14 Jul 2026 00:00:00 -0400

Series Type : Other ; Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencing ; Third-party reanalysis
Organism : Mus musculus

This SuperSeries is composed of the SubSeries listed below.

GSE231690 Widespread transmission of DNA supercoiling and selective topoisomerase utilization regulates torsional stress within the neuronal genome [RNA-Seq]

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Amir Segev ; Ilse D Ramirez ; Lahiri Konada ; Morgan Crewe ; Ram Madabhushi
Series Type : Expression profiling by high throughput sequencing ; Third-party reanalysis
Organism : Mus musculus

DNA supercoiling has the potential to alter gene transcription and chromatin topology, yet how its distribution is regulated on a genome-wide level is poorly understood. Here we utilized psoralen crosslinking and sequencing (TMP-seq) to assess the distribution of underwound DNA at high resolution in postmitotic neurons. We report that supercoiling propagates widely (> 200 kb) from the sites of active RNAPII and that its distribution is constrained by chromosome compartments and by specific nucleosome configurations, including H3K27me3-rich regions and broad distributions of active promoter-related chromatin marks. Underwound DNA does not accrue upstream of expressed genes in postmitotic neurons, which could shield them from cumulative torsional stress. Inhibiting either transcription or TOP1 affect underwound DNA levels genome-wide; however, supercoiling at the boundaries of expressed genes is minimally perturbed, indicating that dynamic supercoiling is not locally confined to sites of RNAPII activity at expressed genes. Surprisingly, TOP1 inhibition elevates supercoiling but stimulates nascent transcription at most genes and other sites of transcription, including enhancers, suggesting that torsional stress generally favors transcription, and that topoisomerase activity is not essential for transcription at most genes. We show that the induction of cryptic transcription within gene bodies, and not supercoiling buildup, could underlie the vulnerability of long neuronal genes to topoisomerase inhibition. These observations illuminate how chromatin organization governs the distribution of torsional stress within the genome and how the interplay of supercoiling and topoisomerases regulates transcription.

GSE231610 Widespread transmission of DNA supercoiling and selective topoisomerase utilization regulates torsional stress within the neuronal genome [TOP2Bcc-seq]

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Amir Segev ; Ilse D Ramirez ; Lahiri Konada ; Morgan Crewe ; Ram Madabhushi
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

GSE231609 Widespread transmission of DNA supercoiling and selective topoisomerase utilization regulates torsional stress within the neuronal genome [fastGRO-seq]

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Amir Segev ; Ilse D Ramirez ; Lahiri Konada ; Morgan Crewe ; Ram Madabhushi
Series Type : Other
Organism : Mus musculus

GSE231608 Widespread transmission of DNA supercoiling and selective topoisomerase utilization regulates torsional stress within the neuronal genome [TMP-Seq]

Tue, 14 Jul 2026 00:00:00 -0400

Contributors : Amir Segev ; Ilse D Ramirez ; Lahiri Konada ; Morgan Crewe ; Ram Madabhushi
Series Type : Other
Organism : Mus musculus