New GEO Series

GSE328849 Spatial transcriptomics identifies IL-32 as a lipid droplet-associated cytokine linked to tubular injury in human diabetic kidney disease [GeoMx]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Kieran Meadows ; Hyunjae Chung ; Son Vo ; Aysa Imanzadeh ; Heewon Seo ; Sisay G Belay ; Asha Swamy ; Wulin Teo ; Kevin Chapman ; Graciela Andonegui ; Hallgrimur Benediktsson ; Peter K Stys ; Thang Pham ; Daniel A Muruve ; Justin Chun
Series Type : Other
Organism : Homo sapiens

Diabetic kidney disease (DKD) is a severe complication of diabetes mellitus and the leading cause of chronic kidney disease worldwide. Among the many drivers of tubular injury, lipid accumulation and inflammation are emerging as major contributors to kidney disease progression, but the molecular link between lipid metabolism and inflammatory signaling remains to be determined. Kidney biopsies from patients with DKD across pathologic classes were labelled for lipid droplets and analyzed by Nile Red spectroscopy. Digital spatial profiling and single-cell spatial transcriptomics were performed on samples from 14 patients representing different DKD classes. RNA scope and immunofluorescence microscopy were used for data validation and characterization. Lipid droplets (LD) were increasingly abundant in advanced stages of DKD, primarily accumulating in the proximal tubules. Single-cell spatial transcriptomics identified several genes—DUSP5, AZU1, COL9A1, HSPB1, and IGFBP7—as highly upregulated in DKD. Remarkably, IL32, which encodes a LD-associated cytokine, was highly enriched in injured proximal tubules. Immunofluorescence confirmed IL-32 localization to LDs predominantly within KIM1 positive tubules in moderate to advanced DKD. Furthermore, injured IL-32 expressing tubules were in close proximity to infiltrating neutrophils and macrophages, immune effectors of non-resolving inflammation and kidney disease progression. IL-32 is a LD-associated cytokine upregulated during tubular injury that represents a potential link between lipid dysregulation, inflammation and progression in human DKD.

GSE328831 Bulk RNA-seq of laser-microdissected granuloma and adjacent non-granuloma regions from FFPE lung tissues of pulmonary sarcoidosis

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Koji Murakami ; Kento Fujiwara ; Tsutomu Tamada
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Sarcoidosis is a systemic granulomatous disease with heterogeneous organ involvement and clinical outcomes. To characterize transcriptional features associated with pulmonary sarcoid granulomas, we performed bulk RNA sequencing of laser-microdissected granuloma regions and adjacent non-granuloma regions from formalin-fixed paraffin-embedded (FFPE) lung tissue specimens obtained from patients with pulmonary sarcoidosis. The dataset includes paired regional samples derived from clinically obtained lung specimens. These data provide a resource for investigating localized gene expression differences associated with granuloma formation in pulmonary sarcoidosis.

GSE328810 Episignatures associated with 8-week combined physical exercise in women with obesity

Thu, 23 Apr 2026 00:00:00 -0400

Series Type : Methylation profiling by array
Organism : Homo sapiens

Aims: Obesity is influenced by epigenetic mechanisms; however, little is known about DNA methylation markers associated with exercise-induced health-promotion interventions. This aims to explore the episignatures of an 8-week combined physical exercise training protocol on DNA methylation patterns in women with obesity. Patients and Methods: Thirteen women with obesity (BMI: 33 ± 2 kg/m²; age: 34 ± 5 years) underwent assessments of body composition, waist circumference, physical performance (VO₂max), and peripheral blood collection before and after an 8-week combined physical training intervention (3 sessions/week, 55 minutes/session, 70-90% maximum heart rate). DNA methylation was analyzed using the Illumina EPIC BeadChip. Results: The intervention improved clinical outcomes, including reduced waist circumference and increased VO₂max (p < 0.05). Epigenome-wide analysis identified 15 differentially methylated regions, highlighting hypomethylation in SLFN11 and PM20D1 hypermethylation in GATA5. These genes are involved in pathways related to immune response, tumor suppression, thermogenesis, metabolic regulation, adiposity, glucose homeostasis, and transcriptional control. Conclusion: Combined physical training induced clinical improvements and DNA methylation changes in women with obesity, suggesting that exercise may alter the episignatures related to obesity.

GSE328760 Nanoparticle-enabled tuning of cell density for enhanced adhesion and tissue repair

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Hyun Su Park ; Gwang-Bum Im ; Joung Wook Bae ; Suk Ho Bhang
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Low retention of transplanted stem cells at target sites remains a major barrier to clinical translation. Conventional strategies — including genetic modification, chemical functionalization, and biomaterial encapsulation — often face limitations in translational feasibility, safety, or procedural complexity. Here, we present a nanoparticle-enabled biophysical approach to enhance cell retention. Cell-settling nanoparticles (CN), composed of clinically approved materials, are rapidly incorporated into mesenchymal stem cells (MSCs), increasing cellular density to accelerate gravitational settling and improve adhesion and survival. Building on this, we develop copper-chaperone-activatable nanoparticles (CCN), which enhance tissue regeneration and anti-fibrotic signaling through activation of fibroblast growth factor 2 (FGF2) and a positive feedback loop. In a mouse skin wound model, CCN-treated MSCs exhibit enhanced vascularization and reduced fibrosis. These findings demonstrate that modulation of cellular density and physical forces can improve stem cell engraftment, establishing a biophysical framework for safe and translationally relevant cell-based therapies.

GSE328709 Type I interferon signaling in microglia drives synaptic engulfment and neuronal loss following traumatic brain injury

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Brittany P Todd ; Zili Luo ; Molly J Larson ; Polly J Ferguson ; Alexander G Bassuk ; Elizabeth A Newell
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Type I interferon (IFN‑I) signaling has emerged as a central regulator of neuroinflammation across diverse central nervous system disorders, including traumatic brain injury (TBI). While TBI is a leading cause of neurologic morbidity and mortality through young adulthood, there is a paucity of neuroprotective therapies available to clinicians. Recent work has demonstrated neuroprotection after global IFN-I deficiency, yet the cell‑type‑specific contributions to traumatic brain injury (TBI) and the mechanisms of immune modulation remain poorly defined. Using mice with microglia‑specific IFN‑I receptor deficiency, we show that loss of microglial IFN‑I responsiveness suppresses microglial reactivity, reducing microglial accumulation, synaptic engulfment, antigen presentation, and T cell interactions after TBI. This attenuation preserves neuronal integrity and limits thalamic neuronal loss. However, despite this neuroprotection, microglia‑restricted IFN‑I blockade reveals functional redundancy across CNS cell types, underscoring the multi-cellular nature of IFN‑I signaling in the injured brain. Together, our findings delineate a microglial IFN‑I–dependent pathway that exacerbates secondary injury after TBI and highlight both the therapeutic potential and inherent limitations of cell‑type‑targeted IFN‑I modulation.

GSE328637 The GET Pathway Modulates Azole Susceptibility through Sterol Metabolic Remodeling and Protein Trafficking in Filamentous Fungi

Thu, 23 Apr 2026 00:00:00 -0400

Contributor : Shuting Ye
Series Type : Expression profiling by high throughput sequencing
Organism : Neurospora crassa

Azole antifungals are widely used to control fungal infection, yet resistance mechanisms beyond drug efflux and target modification remain insufficiently understood. Here, we identified the Guided Entry of Tail-anchored proteins (GET) pathway as a conserved regulator of azole susceptibility in Neurospora crassa and Aspergillus fumigatus. Deletion or dysfunction of the core GET components Get-3 or Get-4 confers resistance to multiple azoles without impairing hyphal growth or sporulation. Mechanistically, GET deficiency neither reduced intracellular accumulation nor altered drug efflux and target expression or total ergosterol levels. Instead, GET-deficient strains displayed significantly reduced accumulation of the toxic sterol intermediate 14α-methyl-3,6-diol under azole stress, indicating a potential bypass of azole-induced sterol toxicity. Proximity labeling and functional validation indicated that GET deficiency perturbs the trafficking of multiple azole-resistance-associated proteins, including the key tail-anchored protein transporter Emp-47 and mitochondrial Cox subunits Cox-4 and Cox-15, which deletion enhanced azole resistance. Transcriptomic and functional analysis further revealed that GET disruption altered the expression of some azole resistance-associated genes, which involve in membrane transport, metabolism, and cell wall organization, independent of canonical stress pathways. In this study, a total of 17 new genes that modulate azole susceptibility were identified. Collectively, our findings uncover a non-classical mechanism of azole resistance mediated by GET-dependent protein trafficking and metabolic adaptation, conserved across filamentous fungi.

GSE328573 Photosensitizer DTP Co-Administered with Statins Potentiates Renal Carcinoma Therapy by Modulating Cholesterol to Enhance PDT.

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Jianqiao Li ; Yuankang Feng ; Yong Wang ; Dan Yue ; Ge Hong ; Shiyue Zhang ; Shumin Yu
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Renal cell carcinoma (RCC) is the most common histological subtype of kidney cancer. Although targeted therapies and immune checkpoint inhibitors have markedly improved patient outcomes, their efficacy remains limited. In recent years, photodynamic therapy (PDT) has drawn increasing attention for its role in cancer treatment. To investigate the effects of the novel porphyrin-based photosensitizer meso-5-[ρ-DTPA-aminophenyl]-10,15,20 triphenylporphyrin (DTP) on RCC, we employed the human renal tubular epithelial cell line HK-2, human RCC cell lines 786-O, ACHN, and A498, as well as the murine renal carcinoma cell line Renca. We assessed intracellular DTP uptake, phototoxicity, and subcellular localization, and further explored potential mechanisms through next-generation sequencing. Our results showed that DTP uptake was significantly higher in RCC cells than in normal renal tubular epithelial cells, and DTP-PDT exerted pronounced phototoxic effects on RCC cells. Through sequencing and in vitro analyses, we found that DTP-PDT markedly reduced cholesterol levels in RCC cells while inducing compensatory upregulation of HMGCR. In vivo experiments further demonstrated that combining DTP-PDT with statins produced stronger anticancer effects. Overall, this study provides compelling evidence that DTP-PDT exhibits potent cytotoxic activity against renal cell carcinoma, and that statins can further enhance its therapeutic efficacy.

GSE328526 Eosinophil-derived COX-2 protects against experimental colitis through the PGE2–IL-22 axis

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Yang Yang ; Cynthia Ju
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Inflammatory bowel disease (IBD) is driven by a breakdown in immune regulation and epithelial barrier function, yet the contribution of eosinophils to this process has remained poorly defined and controversial. While eosinophils infiltrate the intestinal mucosa during both flares and remission, their role in shaping disease outcomes is unclear. Our RNA-seq analyses of colonic eosinophils isolated from dextran sulfate sodium (DSS)-treated mice revealed a significant upregulation of cyclooxygenase (COX)-2 (gene name, Ptgs2). Eosinophil-specific deletion of COX-2 (Ptgs2fl/fleoCre+/−) reduced IL-22 production and exacerbated DSS- and trinitrobenzene sulfonic acid (TNBS)-induced colitis, characterized by greater weight loss, higher disease activity, colon shortening, and epithelial injury. Administration of recombinant IL-22 reversed these phenotypes. Mechanistically, eosinophil-derived COX-2 enhanced IL-22 production by type 3 Innate lymphoid cells (ILC3s) through prostaglandin E2 (PGE2) signaling. Consistently, Ptgs2fl/fleoCre+/− mice exhibited reduced colonic PGE2 levels, while PGE2 analog treatment restored IL-22 production and mucosal protection. Our findings identify eosinophil-derived COX-2 and PGE2 as a critical regulator of IL-22 production during colitis, uncovering a eosinophil–ILC3 cross talk that safeguards the intestinal barrier and represents a promising therapeutic target in IBD.

GSE328515 RNA-seq analysis of lenvatinib-sensitive and lenvatinib-resistant tumor tissues from a subcutaneous HCC mouse model

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Yunkai Lin ; Xiaomeng Wang
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

To investigate the molecular mechanisms underlying acquired resistance to lenvatinib in hepatocellular carcinoma (HCC), we established a lenvatinib-resistant mouse model using H22 cell-based subcutaneous xenografts. Tumor tissues were collected from lenvatinib-sensitive (H22-NR) and lenvatinib-resistant (H22-LR) mice. We performed RNA-sequencing to identify differentially expressed genes and signaling pathways that mediate lenvatinib resistance. Comparative gene expression profiling analysis between the NR and LR groups was conducted to screen for key drivers of drug resistance.

GSE328508 High-throughout sequencing of ovarian cancer cells treated with T-oligo

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Jiaying Tong ; Yeying He ; Xiaohui Zheng
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

After treating human ovarian cancer cells ES2 with T-oligo G4+RHPS4, high-throughput sequencing technology was employed. The transcriptome analysis revealed that T-oligo G4+RHPS4 does not exert its anti-tumor effect solely through telomere dysfunction, but instead simultaneously regulates cell cycle, senescence, and metabolic-related signaling pathways, thereby synergistically inducing the death of ovarian cancer cells.

GSE328424 Ductal Epithelial MXD3 Promotes Disease Progression in Acute Pancreatitis through Wnt/b-catenin-Mediated Inflammation and Injury

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Xianru Jia ; Bingbing Cui ; Xuejin Liu
Series Type : Expression profiling by high throughput sequencing ; Third-party reanalysis
Organism : Rattus norvegicus

Acute pancreatitis (AP) is a severe inflammatory disease where epithelial injury and dysregulated repair are central to pathogenesis, yet the underlying transcriptional mechanisms remain poorly understood. This study employed an integrated approach to identify and characterize the transcription factor MXD3 as a master regulator of AP progression. Using single-cell RNA sequencing in a cerulein-induced rat AP model, we delineated a pathogenic epithelial trajectory from ciliated through non-ciliated to a proliferative state, with MXD3 emerging as the most significantly upregulated transcription factor in the proliferative cluster. Subsequent validation in pancreatic ductal epithelial-specific MXD3 knockout rats revealed profound protection against AP, manifesting as reduced histological damage, diminished fibrosis, attenuated neutrophil infiltration (MPO+ cells), and decreased expression of pro-inflammatory cytokines (IL-6, TNF-a, IL-1b). Mechanistically, we demonstrated that MXD3 directly activates the Wnt/b-catenin pathway, as evidenced by increased non-phospho b-catenin, its nuclear accumulation, and transcriptional upregulation of canonical targets (c-Myc, Cyclin D1, Axin2). Furthermore, functional rescue experiments confirmed the pathway's necessity, wherein the b-catenin inhibitor ICG-001 substantially reversed MXD3-driven apoptosis, necrosis, and pro-inflammatory cytokine secretion (IL-1b, IL-6, MCP-1) in vitro. Our findings establish a novel MXD3-Wnt/b-catenin axis as a crucial mechanism governing epithelial pathology in AP, revealing MXD3 as a promising therapeutic target for this debilitating condition.

GSE328279 Bulk RNA sequencing in Mouse Bone Marrow-Derived Macrophages Following CD74 Deficiency

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Rui Peng ; Bo Yu ; Lutian Yao ; Lei Zhang ; Tao Gui
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Following CD74 knockout in mouse bone marrow-derived macrophages (BMDMs), we employed bulk RNA sequencing to systematically profile transcriptomic changes, with a particular focus on alterations in key regulatory elements. Building on these findings, we further investigated the potential molecular mechanisms through which CD74 modulates signaling pathways in macrophages, aiming to uncover its regulatory roles in immune responses and macrophage functional plasticity.

GSE328242 Precision Editing of Cyclophilin A Generates Cyclosporine and Voclosporin Resistant Cellular Therapies

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Holly Wobma ; Francesca A Calderon ; Jiayi Dong ; Kayleigh Omdahl ; Xianliang Rui ; Elisa J Rojas Palato ; Rene S Bermea ; Alexandre Albanese ; Franziska Wachter ; Marlana Winschel ; Katherine A Michaelis ; William A Burns ; Gillian Selig ; Lorenzo Cagnin ; Victor Tkachev ; Susan E Prockop ; Peter A Nigrovic ; Bruce R Blazar ; Ulrike Gerdemann ; Leslie S Kean
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Recipients of allogeneic transplants or patients with autoimmune disease require immune suppression, often with calcineurin inhibitors. There is an expanding repertoire of immune effector cell therapies, including CD19 CAR-T cells and viral-specific T cells, deployed in these patients; however, ongoing calcineurin inhibition may be detrimental to cell therapy function. We developed a CRISPR/Cas9-based approach to engineer dual cyclosporine/voclosporin resistant cell therapies by targeting PPIA (encoding cyclophilin A), a critical binding partner for both drugs. Because Cyclophilin A has homeostatic functions in T cells, a complete knock-out is detrimental to cell viability. We thus targeted its C-terminus, disrupting drug binding while leaving the majority of the protein intact. C-terminal editing was stable throughout expansion and preserved Cyclophilin A expression. Edited CD19 CAR-T cells retained effector function in the presence of cyclosporine and voclosporin, including proliferation, cytokine production, and target cell killing, resulting in improved survival in murine models of CD19+ leukemia. Edited CMV-specific T cells also demonstrated preserved antigen-specific proliferation and cytokine production in the presence of these drugs. C-terminal editing of Cyclophilin A offers a promising avenue for developing next-generation cell therapies for patients receiving calcineurin inhibitors.

GSE327708 In vivo systematic detection of the outcomes of CRISPR/Cas9 mediated DNA repair in skeletal muscle stem cells

Thu, 23 Apr 2026 00:00:00 -0400

Series Type : Other ; Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

This SuperSeries is composed of the SubSeries listed below.

GSE327580 Acquired genetic and cell state changes in IDH-mutant glioma progression [snATAC]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Kevin C Johnson ; Avishay Spitzer ; Frederick S Varn ; Masashi Nomura ; Luciano Garofano ; Anna Lasorella ; Mario L Suvà ; Antonio Iavarone ; Itay Tirosh ; Roel G Verhaak
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens

Isocitrate dehydrogenase (IDH)-mutant gliomas are malignant brain tumors that typically arise in early- to mid-adulthood and nearly always recur following treatment. However, the genetic and cellular state changes that drive IDH-mutant glioma progression under treatment remain incompletely understood. Here, we integrated single-nucleus transcriptomic profiles, chromatin accessibility profiles and bulk DNA/RNA sequencing from 75 temporally separated gliomas across 35 patients comprising both the oligodendroglioma and astrocytoma IDH-mutant glioma tumor types. We show that malignant cell states transcriptionally resemble stages of normal glial-neuronal lineage development or a reactive mesenchymal-like state, mirroring states previously described in IDH-wildtype glioblastoma. Malignant cell states displayed distinct chromatin accessibility profiles that were comparable between both IDH-mutant glioma types. The abundance of less differentiated malignant cells increased with grade and with genetic alterations such as PDGFRA amplification. Longitudinal analysis highlighted two major malignant cell state transition patterns. First, reduced lineage differentiation and increased proliferative malignant cells at recurrence were pronounced in gliomas that acquired recurrence-associated genetic events, including treatment-associated hypermutation, increased copy number changes, and cell cycle alterations. Second, increased mesenchymal-like state abundance occurred independently of acquired genetic alterations and instead coincided with heightened macrophage expression. Overall, our findings provide an integrative model that traces the cell-intrinsic and extrinsic factors that shape cellular states during IDH-mutant glioma disease progression.

GSE327392 In vivo systematic detection of the outcomes of CRISPR/Cas9 mediated DNA repair in skeletal muscle stem cells [IDM-Seq long-read]

Thu, 23 Apr 2026 00:00:00 -0400

Series Type : Other
Organism : Mus musculus

CRISPR/Cas9 has revolutionized genome editing with broad therapeutic applications, yet its repair patterns in vivo remain poorly understood. Here, we systematically profile CRISPR/Cas9 editing outcomes at 95 loci using our established CRISPR/Cas9/AAV9-sgRNA system in skeletal muscle stem cells (MuSCs). Through comprehensive characterization of the repair outcomes, our findings demonstrate that the general rules governing CRISPR/Cas9-mediated editing in vivo largely align with those observed in vitro. Additional to the anticipated small editing indels such as MMEJ mediated deletions and NHEJ mediated templated insertions, we uncover a prevalent occurrence of large on-target modifications, including large deletions (LDs) characterized by microhomology (MH) and large insertions (LIs). Notably, the LIs comprise not only exogenous AAV vector integrations but also endogenous genomic DNA fragments (Endo-LIs). Endo-LIs preferentially originate from active genomic regions, with their integration shaped by three-dimensional chromatin architecture. By disrupting key components of the NHEJ and MMEJ repair pathways in vivo, we identify their distinct roles in regulating the large on-target modifications. Together, our work systematically profiles the CRISPR/Cas9 repair outcomes in vivo and offers valuable guidance for improving the safety of CRISPR/Cas9-based gene therapies.

GSE327391 In vivo systematic detection of the outcomes of CRISPR/Cas9 mediated DNA repair in skeletal muscle stem cells [control]

Thu, 23 Apr 2026 00:00:00 -0400

Series Type : Other
Organism : Mus musculus

GSE327245 Effects of GOLPH3 knock-out on the mouse liver transcriptomic profile

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Anastasia Theodoropoulou ; Anita Nasrallah ; Luciano A. Abriata ; Laurence Abrami ; Juliane Da Graca ; Irmak Kaysudu ; Francesco Talotta ; Maria J. Marcaida ; Muhammad U. Anwar ; Ondrej Kovac ; Sergey Y. Vakhrushev ; Alejandro Calleja ; Sylvia Ho ; Antonino Asaro ; Francisco S. Mesquita ; Leila Alieh ; Charlotte Gehin ; Lucie Bracq ; Nika Gorsek ; Sarah Vacle ; Arthur Samurkas ; Alessio Prunotto ; Miroslav Machala ; Olaia Naveiras ; Katrine T. Schjoldager ; F. Gisou Van der Goot ; Matteo Dal Peraro ; Giovanni D'Angelo
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The Golgi complex serves as the central hub of the biosynthetic pathway, where anterograde and retrograde trafficking converge. How cargo and Golgi-resident proteins traverse this organelle has long been debated. Recent studies have identified a molecular machinery that sorts resident proteins into retrograde-directed COPI vesicles during cisternal maturation. Golgi phosphoprotein 3 (GOLPH3) is a key component of this system; however, its physiological relevance and regulatory mechanisms remain poorly defined. Here, we show that GOLPH3 depletion in mice alters both protein and lipid glycosylation, causes partially penetrant embryonic lethality and severely impairs growth and bone mineralization. At the molecular level, we find that GOLPH3 is regulated by functionally antagonistic S-acylation events that control the topology of its membrane association. To mediate retrograde trafficking of Golgi-resident glycosyltransferases, GOLPH3 must bind their cytosolic tails. This occurs via a negatively charged surface region, which is correctly oriented only in one of the S-acylated GOLPH3 conformations. Together, these findings reveal a lipid-mediated regulatory mechanism for intra-Golgi trafficking and establish the critical role of GOLPH3 in vertebrate development.

GSE326423 Complement-regulated Homeostatic Proliferation Controls Memory B Cell Longevity and Repertoire Composition

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Evan Cody ; Peter S Heeger ; David Dominguez-Sola
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Memory B cell (Bmem) survival is essential for guarding against reinfection, yet processes ensuring their longevity remain unclear. As decay-accelerating factor (DAF, CD55), a negative regulator of complement activation, is requisitely downregulated on germinal center B cells and is re-expressed on Bmem, we investigated the effects of deleting DAF on murine (B1-8hi) Bmem in competitive settings. Kinetic analysis showed a progressive reduction in DAF-/- Bmem numbers over six weeks, without affecting Bmem production, pool size, or their ability to respond to rechallenge. Following transfer into unimmunized hosts, wild-type Bmem proliferated to maintain stable Bmem pool sizes, outcompeting DAF-/- Bmem, reflecting homeostatic proliferation. Reduced proliferation and increased cell death in DAF-/- Bmem associated with transcriptional differences in metabolism and migration pathways. Wild type Bmem proliferation increased in C3-/- hosts, and vaccination with a heterologous antigen, which induces local complement activation, locally inhibited bystander B1-8hi Bmem proliferation. Thus, complement-dependent regulation of Bmem homeostatic proliferation influences Bmem longevity and repertoire composition in mice.

GSE326221 Acquired genetic and cell state changes in IDH-mutant glioma progression [snRNA-seq]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Kevin C Johnson ; Avishay Spitzer ; Frederick S Varn ; Masashi Nomura ; Luciano Garofano ; Anna Lasorella ; Mario L Suvà ; Antonio Iavarone ; Itay Tirosh ; Roel G Verhaak
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

GSE326070 Interleukin-34 induced Arg1+ macrophages play a key role in breast cancer brain metastasis.

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Xiaoqing Cheng ; Khooshbu Kantibhai Patel ; Maureen Highkin ; Vaibhav Jain ; Simon Gregory
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

We use 10x Genomics to perform the Single cell RNA sequencing result shows cell type clusters and percentage of the corresponding cell types in the HP organoids that we used for our model.

GSE325996 Interleukin-34 induced Arg1+ macrophages play a key role in breast cancer brain metastasis

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Xiaoqing Cheng ; Khooshbu Kantibhai Patel ; Vaibhav Jain ; Simon Gregory
Series Type : Other
Organism : Mus musculus

We use 10x Genomics to perform the visium RNA sequencing on two tumor tissue, which showed cell type clusters and whole genome profiling in each cell clusters. Visium CytAssist Spatial Gene Expression kit was used for FFPE (Mouse Transcriptome, 6.5 mm, 4 rxns, PN-1000521,10x Genomics).

GSE324860 Acquired genetic and cell state changes in IDH-mutant glioma progression [organoids]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Kevin C Johnson ; Tanyeri Barak ; A. Gulhan Ercan-Sencicek ; Ayse Buket Peksen ; Linbin Zhang ; Jennifer Moliterno ; Roel Verhaak
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

GSE324158 Single-cell multi-omic and spatial landscape of primate pineal gland reveals circadian and melatonin regulatory architecture

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Jihong Zheng ; Yuchen Xiao ; Jianjun Lyu ; Hongtao Xu ; Yaqun Zhang ; Yanchuan Li ; Yihao Li ; Tianjun Wang ; Liu Liu ; Lingjing Jin ; Xuhui Zhou ; Chao Zhang
Series Type : Other ; Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencing
Organism : Macaca fascicularis

The mammalian pineal gland maintains circadian rhythms and homeostasis by secreting melatonin. However, the lack of a cell-resolved regulatory map limits our understanding of how these neuroendocrine functions are orchestrated in primates. Here, we constructed a multi-omics atlas of the Macaca fascicularis pineal gland by integrating snRNA-seq, snATAC-seq, and spatial transcriptomics. We identified pinealocytes as the predominant cell type, alongside six glial and vascular lineages. Chromatin accessibility analysis delineated cell-type-specific regions enriched for melatonin synthesis and phototransduction genes. Notably, we resolved a dual-layer regulatory architecture: while melatonin synthesis programs are robustly organized, circadian clock regulators exhibit a distinct, sparse spatial pattern. Co-expression networks further identified core modules and regulatory hubs—including CRX/OTX2, LHX4, and RORA—that integrate these circadian and light-responsive signals. Cell-cell communication analysis identified signaling axes, such as PTN-ALK/SDC2, RA-RORB, and NRG1-ERBB4, that potentially coordinate this spatial functional organization. Integrating genetic traits showed that sleep and neuropsychiatric risk variants preferentially map to these pineal regulatory modules. Specifically, sleep-associated loci converged on MEIS1-linked elements, while bipolar disorder-associated loci highlighted candidate genes RDH12 and SDK2. Overall, this study reveals the cellular diversity and spatial regulatory logic of the primate pineal gland, providing a foundation for investigating circadian and neuroendocrine regulation in health and disease.

GSE324146 H3 dopaminylation and CaMKII modulate diffuse midline glioma response to CDK9 inhibition

Thu, 23 Apr 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens

Aberrant neurotransmitter signaling and transcriptional dysregulation are hallmarks of gliomagenesis and represent potential therapeutic targets. Monoamine neurotransmitters such as dopamine and serotonin primarily activate GPCRs but can also function epigenetically as histone H3 modifications. Here, we uncover mechanisms of crosstalk between monoamine neurotransmitter signaling, H3 dopaminylation, and RNA polymerase II (Pol2) transcription in diffuse midline glioma (DMG). We find that co-treatment with Pol2 targeting CDK9 inhibitors (CDK9i) and FDA approved neuropsychiatric drugs, including selective serotonin reuptake inhibitors (SSRIs), synergistically reduces DMG growth. Mechanistically, CDK9i+SSRI treatment alters H3 dopaminylation patterns and represses synaptic and neurodevelopmental gene transcription associated with CDK9i resistance. Further phospho-proteomic analyses show that CDK9i monotherapy activates pro survival CaMKII signaling, which can be suppressed by co-treatment with neuromodulatory drugs. These studies establish roles for H3 dopaminylation and neurotransmitter signaling in DMG gene regulation and response to CDK9i, suggesting that monoamine neurotransmitter pathways may be exploited as a therapeutic strategy for DMG.

This SuperSeries is composed of the SubSeries listed below.

GSE322712 Distinct activity in prefrontal projections promotes temporal control of action

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Xin Ding ; Trevor C Butler ; Jon M Resch ; Nandakumar S Narayanan ; Matthew A Weber ; Alexandra S Bova ; Stephanie Guerrero ; Rachel C Cole ; Christopher Hunter ; Hannah R Stutt ; Madison McMurrin ; Mackenzie M Spicer ; Mackenzie M Conlon ; Shane A Heiney ; Youngcho Kim
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Prefrontal neurons can have diverse activity during cognitive functions such as working memory, attention, and timing; however, the importance of this heterogeneity is unclear. Our goal was to better understand the diversity of prefrontal activity through anatomical connectivity. We harnessed circuit-specific tools in mice to capture activity within prefrontal projections during interval timing, a highly translational cognitive process that requires working memory for temporal rules and attention to the passage of time to estimate a temporal interval of several seconds. We used neuronal recordings to capture prefrontal activity during interval timing, with major patterns characterized by monotonic time-dependent ramping over a temporal interval. We then leveraged retrograde viruses to interrogate prefrontal cortex (PFC) projections to the mediodorsal thalamus (PFC-MD) and to the dorsomedial striatum (PFC-DMS). We report three novel results. First, circuit-specific calcium fiber photometry revealed that PFC-MD and PFC-DMS activity encoded distinct temporal signals, with PFC-MD projections ramping down and PFC-DMS ramping up to interval timing response times. Second, circuit-specific inactivation revealed that PFC-DMS inactivation disrupted animals’ internal estimates of time. Third, circuit-specific single-nucleus RNA sequencing of prefrontal projections revealed distinct transcriptomic profiles between PFC-MD and PFC-DMS projections, with enriched genes for cortical layers as well as genes such as Cux2, Camk2n1, Htr4, and Foxp2. These data suggest differences in gene expression and connectivity distinguish prefrontal activity during interval timing. These findings advance our fundamental understanding of prefrontal function and dysfunction in human disease.

GSE320046 HNF4a controls growth, identity and response to KRAS inhibition in IMA [ATAC-seq]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Headtlove Essel Dadzie ; Eric L Snyder
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

Cellular plasticity is a key feature of cancer that enables tumor cells to switch lineage identities, driving disease progression and resistance to therapy. In invasive mucinous adenocarcinoma (IMA), a pronounced pulmonary-to-gastric lineage switch occurs as NKX2.1 is lost and HNF4α, a master regulator of gastric differentiation, is upregulated. Although absent in normal alveolar type 2 cells, HNF4α is aberrantly expressed in most IMA tumors. In this study, we investigate the role of HNF4α within established IMAs and find that it directly activates a gastric differentiation program, particularly in pit cells. Loss of HNF4α disrupts this program and permits FOXA1 and FOXA2 to bind new regulatory sites, leading to the upregulation of neuronal and liver-like gene modules. In light of the poor response of mucinous tumors to KRAS inhibitors, we investigated whether HNF4α modulates sensitivity to KRASG12D targeted therapy. Treatment with MRTX1133 revealed that loss of HNF4α significantly increases IMA sensitivity by reducing the IC50 in vitro and enhancing tumor regression in vivo. Mechanistically, HNF4α deletion impairs cell-cycle progression in drug-tolerant persister cells, while tumors retaining HNF4α maintain these cell-cycle regulators despite KRAS inhibition, promoting persister cell survival. Our findings establish HNF4α as a critical driver of IMA biology governing both gastric differentiation and resistance to KRAS inhibitors and support the development of combination strategies to overcome therapeutic resistance in IMA.

GSE319518 Gene expression profiling of HepG2 cells with or without SAMD4B overexpression

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Junji Otani ; Miki Nishio ; Makoto Nishimori ; Tomohiko Maehama ; Akira Suzuki
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

The transcriptional cofactors YAP1 and TAZ regulate target gene expression by binding to the transcription factor TEAD. Due to their roles in cancer initiation, progression, and drug resistance, YAP1 and TAZ are promising targets for cancer therapy. SAMD4A/B are RNA-binding proteins that are broadly expressed across human tissues, but few of their molecular targets and biological functions have been identified. In Drosophila, the SAMD4A/B homolog Smaug participates in early embryonic development by disrupting the stability and translation of maternal mRNA. To discover targets inhibiting the YAP1/TAZ-TEAD oncogenic transcription program, we screened a whole-genome siRNA library and identified siSAMD4B as potently suppressing TEAD activity in human cancer cells. We showed that SAMD4A/B increased TEAD activity by destabilizing and repressing the translation of VGLL4 mRNA, promoting cancer progression in vitro. Conversely, inhibiting either SAMD4A or SAMD4B elevated VGLL4 mRNA, which suppressed TEAD activity and inhibited cancer progression. Notably, transgenic mice expressing liver-specific SAMD4B exhibited accelerated development of intrahepatic cholangiocarcinomas in an Nf2-deficient background. These tumors appeared in the mutants at one week of age and caused death due to hepatic failure by 100 days. Thus, SAMD4A/B may be a promising target for anticancer drugs designed to inhibit TEAD activation.

GSE319418 Gene expression profiling of H1299 cells with or without SAMD4A expression

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Junji Otani ; Miki Nishio ; Makoto Nishimori ; Tomohiko Maehama ; Akira Suzuki
Series Type : Expression profiling by array
Organism : Homo sapiens

GSE318876 Systematic discovery of pro- and anti-HIV host factors in primary human CD4+ T cells

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Ujjwal Rathore ; Eli Dugan ; Hunter Thornton ; Vigneshwari E Kumar ; Rama Dajani ; Ryan C Burdick ; Janet M Young ; Zachary Steinhart ; Reanna Lao ; Krista A Delviks-Frankenberry ; Wooyoung Choi ; William S Henriques ; Ignacia Echeverria ; Emma Dann ; Ishaan Dureja ; Nandini Pathak ; Maya M Arce ; Justin McKetney ; Jennifer M Umhoefer ; Simrun Parulekar ; Ralf Schmidt ; Benjamin Polacco ; Jason Neidleman ; Mauricio Montano ; Vinh Q Nguyen ; Andrej Sali ; Jay A Levy ; Jeannette L Tenthorey ; Yifan Cheng ; Nadia R Roan ; Danielle L Swaney ; Robyn M Kaake ; Stacie E Dodgson ; Joseph Hiatt ; Vinay K Pathak ; Harmit S Malik ; Nevan J Krogan ; Alexander Marson
Series Type : Other
Organism : Homo sapiens ; synthetic construct

Host factors that promote or restrict human immunodeficiency virus (HIV) infection in human CD4+ T cells have not been comprehensively identified. We performed orthogonal genome-wide CRISPR activation (CRISPRa) and CRISPR knockout (CRISPRn) screens in primary human CD4+ T cells to systematically discover pro- and anti-HIV host factors. Candidate hits were validated using secondary pooled screens and arrayed perturbations and were further characterized using assays for HIV infection, T cell activation, and HIV receptor/co-receptor expression. CRISPRa identified multiple potent antiviral factors including PI16, PPID, SHISA3, and ITM2A. PI16 interacts with host pathways involved in HIV fusion and inhibits viral entry, while PPID (Cyp40) binds HIV capsid and restricts infection by reducing nuclear import of the HIV core. Structural modeling, evolutionary analyses, and targeted mutagenesis identified domains and residues required for PPID-mediated restriction, including non-human primate ortholog substitutions that enhance antiviral activity. Together, these data define the functional HIV–host interaction landscape in primary human CD4+ T cells and reveal new mechanisms modulating HIV infection.

GSE315798 Transcriptomic profiling of E0771 breast tumors grown in wild-type versus uPAR-deficient hosts

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Mehran Alizadeh Harzevili ; Niaz Mahmood ; Ani Arakelian ; Shafaat Ahmed Rabbani
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The goal of this study is to define the contribution of host-derived urokinase plasminogen activator receptor (uPAR) to the tumor microenvironment in breast cancer. While uPAR is well recognized for its tumor-intrinsic roles, its functions within the host compartment, particularly in shaping immune and stromal responses, remain poorly understood. Using the syngeneic E0771 murine breast cancer model, we compared transcriptomic profiles of primary tumors grown in wild-type versus uPAR-deficient hosts to identify gene expression programs associated with loss of host uPAR. Bulk RNA sequencing was employed to capture global changes in tumor-associated transcriptional networks, with particular emphasis on immune-related pathways, antigen presentation, extracellular matrix remodeling, and tumor–host crosstalk. The objective of this work is to establish host-derived uPAR as a regulator of the tumor microenvironment and to provide a transcriptomic framework linking uPAR deficiency to altered immune contexture and microenvironmental signaling. This dataset is intended to support mechanistic interpretation of tumor–host interactions and to serve as a resource for future studies investigating uPAR-targeted strategies in breast cancer.

GSE313586 RXR Agonist V-125 Induces Distinct Transcriptional and Im-munomodulatory Programs in Mammary Tumors of MMTV-Neu Mice Compared to Bexarotene

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Afrin S Chowdhury ; Lyndsey Reich ; Karen Liby ; Elizabeth Yeh ; Ana Leal
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Background: The retinoid X receptor (RXR) is a ligand-activated nuclear receptor that heterodimerizes with numerous partners to regulate diverse transcriptional programs. RXR agonists, in-cluding the FDA-approved drug bexarotene, show anti-tumor activity but are limited by adverse side effects. V-125 is a next-generation RXR agonist engineered for improved se-lectivity, pharmacokinetics, and reduced lipogenic effects. This study compares the mo-lecular and functional effects of V-125 and bexarotene in HER2⁺ breast cancer models. Methods: Female MMTV-Neu mice bearing mammary tumors were treated with control, V-125 (100 mg/kg diet), or bexarotene (100 mg/kg diet) for 10 days. RNA sequencing was used to identify differentially expressed genes and pathways. Candidate targets were validated by qPCR and immunohistochemistry (IHC). Immune modulation was evaluated by IHC staining for CD8 cells and CD206⁺ macrophages in tumors to capture the tumor microen-vironment. Functional assays in JIMT-1 human HER2⁺ cells assessed RXR target activation and clonogenic potential in tumor cells. Results: V-125 induced broader transcriptional changes than bexarotene, including selective up-regulation of Nrg1, Nfasc, Lrrc26, and Chi3l1 genes associated with improved patient sur-vival. Pathway analysis revealed regulation of immune activation, cancer signaling, and lipid metabolism. Both V-125 and bexarotene suppressed colony formation in JIMT-1 cells, confirming previous observations about RXR-dependent inhibition of tumor cell growth. Moreover, V-125 in vivo had distinct capabilities to increase CD8 cell infiltration and reduced CD206⁺ macrophages, whereas bexarotene did not. Conclusion: V-125 but not bexarotene reprograms tumor transcriptional programs and the immune landscape in an anti-tumor manner in MMTV-neu mouse model and in in vitro models of HER2⁺ breast cancer. This highlights its promise as a selective RXR agonist with anti-tu-mor and immunomodulatory activity in HER2⁺ breast cancer.

GSE312393 Transcriptomic adaptations of human muscle after short- and long-term exercise

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Silvia Campanario ; Mercedes Grima-Terrén ; Megan Rommelfanger ; Stefania Dell’ Orso ; Xuesong Feng ; Ignacio Ramírez-Pardo ; Aina Calls ; Andrés Cisneros ; Kyung Dae Ko ; Esther García-Domínguez ; Laura Pena-Couso ; Grace Chou ; Yuewen Zheng ; Nasun Hah ; Davide Randazzo ; Alberto Pérez-Garcia ; Mari Carmen Gómez-Cabrera ; Tovah E Markowitz ; Iago Pinal-Fernandez ; Andrew Mammen ; Jose Milisenda ; Benjamin Yang ; Antonio L Serrano ; Eusebio Perdiguero ; Vittorio Sartorelli ; Joan Isern ; Pura Muñoz-Cánoves
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

The molecular mechanisms that govern muscle hypertrophy (as induced by increased physical activity) remain incompletely defined. Through RNA-seq of human muscle, we confirm observations from mice that extensive remodeling of the neuromuscular junction (NMJ) occurs in human muscle after exercise.

GSE311567 Transcriptomic adaptations of human muscle in patients with polyarteritis nodosa and muscle denervation

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Iago Pinal-Fernandez ; Andrew Mammen ; Jose Milisenda
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

The molecular mechanisms that govern muscle atrophy (as seen in disuse or aging) remain incompletely defined. Through RNA-seq of human muscle, we confirm observations from mice that extensive remodeling of the neuromuscular junction (NMJ) occurs in human denervated muscle.

GSE310660 PROX1 loss in adult mouse Schlemm’s canal causes permanent ocular hypertension

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Sofia L Ochoa ; Hoi Lam Li ; Hyeohn Kim ; Zihang Yan ; Natalia C Mendonca ; Pan Liu ; Hyunjoo J Lee ; Michael P Vincent ; Hao F Zhang ; Haiyan Gong ; Evan A Scott ; Mark Johnson ; Benjamin R Thomson
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Glaucoma is associated with ocular hypertension and lowering intraocular pressure is a key objective of glaucoma therapies. Recent studies have established a role for the Schlemm’s canal endothelium in this pressure increase and have shown it to have a unique, lymphatic-like, hybrid phenotype. However, the role of these lymphatic phenotypes in the adult canal remains uncertain. Long-term functional studies have been limited by systemic importance of lymphatic genes and lack of Schlemm’s canal–specific animal models. Here, we designed and validated a strategy using 4OH-tamoxifen-loaded nanocarriers to generate targeted, Schlemm’s canal specific knockout mice lacking lymphatic phenotypes. Using this system, we selectively deleted Prox1, the master transcription factor governing lymphatic fate. Within four weeks, intraocular pressure significantly increased, and ocular hypertension was maintained for at least 24 weeks. Unlike lymphatic vessels, which degenerate following Prox1 deletion, Schlemm’s canal reverted to a less functional vein-like phenotype with no change in size or morphology. These results highlight the utility of nanocarriers for tissue-specific genetic recombination and demonstrate that changes in lymphatic phenotypes alter intraocular pressure, providing new targets for glaucoma therapy. Moreover, as we found that PROX1 was downregulated with age in human Schlemm’s canal, these canal-specific conditional Prox1 knockout mice are a valuable new adult-onset model of ocular hypertension that captures key features of age-related human disease.

GSE310103 Runx3 instructs Aire+ mTEC development, TSA gene expression, and central tolerance

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Jun Hyung Sin ; Sloan H Phillips ; Michael R Waterfield
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The transcription factor Runx3 modulates key gene expression programs important for the development of multiple tissues. Here, we uncover new functions for Runx3 in thymic epithelial lineage development and show Runx3 expression in medullary thymic epithelial cells (mTECs) is required for both Autoimmune Regulator + (Aire+) mTEC development and tissue-specific antigen (TSA) gene expression. Consequently, TEC-specific deletion of Runx3 in mice results in a profound decrease in Aire+ mTECs, a global loss of TSA gene expression, and the development of autoimmunity. Moreover, loss of Runx3 in TECs results in an expansion of immature CCL21+ mTECs and a loss of Aire-dependent mimetic cells. Single-cell analysis reveals Runx3 modulates core transcriptional programs in TECs that correlate with the observed cellular changes. Our findings highlight a previously undescribed role for Runx3 in mTEC development and thymic central tolerance.

GSE306092 Patient-Derived Lymphoma Spheroids Reveal Predictive Markers of Glofitamab Resistance in Relapsed/Refractory B-NHL

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Paul Marcoux ; Fabien Gava ; Marie Tosolini ; Pauline Gravelle ; Christine Bezombes ; Camille Laurent
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Bispecific antibodies (bsAbs) such as glofitamab represent a promising therapeutic approach for relapsed/refractory B-cell non-Hodgkin's lymphoma (R/R B-NHL), but resistance mechanisms remain poorly understood. This study aimed to identify predictive markers of bsAbs resistance based on the response of 3D patient-derived lymphoma spheroids (PDLS) established from R/R B-NHL samples. PDLS were treated with 0.1 nM glofitamab for 3 days and B-cell depletion was quantified as measure of ex vivo treatment response. Comprehensive immune profiling were performed on patient samples using multiparametric flow cytometry, single-cell RNA sequencing, CODEX spatial proteomics and functional assays. This study revealed that high responders to glofitamab possessed more activated CD8+ T-cells with higher cytotoxic signatures, while low responders showed enriched exhausted CD8+ T-cell populations with enhanced expression of exhaustion markers (TIGIT, LAG3, PD1). Moreover, low responders demonstrated elevated functional CD4+ T-follicular helper (Tfh) cells in close proximity to malignant B-cell thus promoting their survival through IL21 and CXCL13 signaling pathways. Functional experiments have shown that adding anti-TIGIT co-treatment enhanced glofitamab efficacy in low responder samples, and Tfh depletion improved cytotoxic T-cell function. Our findings identify CD8+ T-cell exhaustion and functionally activated Tfh cells as key resistance mechanisms to glofitamab in R/R B-NHL. Targeting these pathways represents a promising strategy to overcome bsAb resistance and improving therapeutic outcomes.

GSE305486 ATF7ip inhibits the tumor immune response by promoting terminal CD8+ T cell Exhaustion III

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Sujit Kashyap ; Jun Hyung Sin ; Michael R Waterfield
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

CD8+ T cell exhaustion limits the immune response to tumors because of ineffective T cell effector functions. Thus, therapies that inhibit T-cell exhaustion are critical for optimizing cancer treatment. Recent studies have implicated epigenetic proteins in T-cell exhaustion. Here, we identified activating transcription factor 7 interacting protein (ATF7ip) as an epigenetic protein critical for inducing T cell exhaustion. Loss of Atf7ip in CD8+ T cells results in decreased terminal exhaustion and increased numbers of progenitor-exhausted cells in both chronic viral infections and cancer. Owing to decreased exhaustion, Atf7ip-deficiency in CD8+ T cells leads to an enhanced immune response to tumors. Mechanistically, ATF7ip functions to stimulate the deposition of repressive H3K9me3 at critical immune-effector gene loci, such as Il7r and Il2 leading to enhanced exhaustion. Our data suggest that ATF7ip may be a rational target for deletion in adoptive T-cell therapies to reduce CD8+ T-cell exhaustion.

GSE305418 ATF7ip inhibits the tumor immune response by promoting terminal CD8+ T cell Exhaustion II

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Sujit Kashyap ; Jun Hyung Sin ; Michael R Waterfield
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

GSE303977 MECP2 Mutations Rewire Human ESC Fate and Bias Cortical Lineage Commitment II

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Marion Guillon ; Margaux Brin ; Anthony Flamier
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Rett syndrome arises from loss-of-function mutations in the X-linked chromatin regulator MECP2, yet the earliest molecular derailments in human development remain poorly defined. Using isogenic hESC models carrying three patient-derived MECP2 mutations, we followed the transcriptome from pluripotency through neuro-ectoderm, neural stem, and neural progenitor stages and into four-month cerebral organoids. Stage dominated transcriptional variance, but mutants shared a secondary program enriched for synaptic-membrane and extracellular-matrix genes. Single-cell profiling revealed a naïve-like, hyper-proliferative state marked by up-regulation of ZFP42 at ESC stage. Strikingly, EMX1, a cortical radial-glia determinant, was consistently suppressed from the earliest stage onward, and cerebral organoids subsequently generated fewer excitatory neurons in favour of inhibitory and glial lineages. These data chart a continuous developmental trajectory for MECP2-mutant human cells and nominate ZFP42 and EMX1 dysregulation as tractable entry points for dissecting Rett pathogenesis.

GSE303838 MECP2 Mutations Rewire Human ESC Fate and Bias Cortical Lineage Commitment [RNA-Seq]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Marion Guillon ; Margaux Brin ; Anthony Flamier
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

GSE303813 MECP2 Mutations Rewire Human ESC Fate and Bias Cortical Lineage Commitment

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Marion Guillon ; Margaux Brin ; Anthony Flamier
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

GSE303540 In vivo systematic detection of the outcomes of CRISPR/Cas9 mediated DNA repair in skeletal muscle stem cells [sgRNA]

Thu, 23 Apr 2026 00:00:00 -0400

Contributor : Yang Fu
Series Type : Other ; Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

GSE303444 Transcriptional and immune repertoire profiling of mismatch repair-deficient colorectal cancer

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Stephen M Thirdborough ; Sheah Lin Lee
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Colorectal cancers (CRC) with deficient mismatch repair (dMMR) exhibit variable responses to immune checkpoint inhibitors, despite their immunogenic nature. To investigate the molecular basis of this heterogeneity, we performed integrated bulk RNA sequencing and immune repertoire profiling on tumor and adjacent normal mucosa from treatment-naïve dMMR CRC patients. Using weighted gene co-expression network analysis, we identified transcriptional modules associated with T and B cell clonality, immune-metabolic interactions, and therapeutic responsiveness. Our dataset provides a valuable resource for understanding the tumor microenvironment in dMMR CRC and supports the development of biomarkers for patient stratification beyond mismatch repair status.

GSE303217 Mutant TP53 hijacks RNA-splicing factor RBM28 to suppress double-strand RNA triggered antitumor immunity

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Tao Xiang ; Ziyi He ; Xiaoyuan Wang ; Shaosen Zhang ; Shihao Zhu ; Jie Yang ; Xiao Hu
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

TP53 mutation may not only compromise its multifaceted tumor-suppressive functions but confer oncogenic properties. Here, we demonstrate that DNA-binding domain mutations of TP53 unexpectedly confer a transcriptional regulatory function, directly driving RNA-splicing factor RBM28 overexpression. Overexpressed RBM28 excessively splices transposon elements, inhibiting dsRNA formation, thereby suppressing dsRNA-triggered type I IFN signaling and subsequent anti-tumor immunity. We demonstrate in mouse tumorigenesis models and human multi-stage esophageal cancer development that mutp53-driven aberrant RBM28/dsRNA/IFN axis plays a crucial role in cancer initiation, progression and resistance to immune checkpoint blockade (ICB) therapy through innate immune suppression. Pan-cancer analysis indicates that this mechanism underlies ICB resistance in most cancers. Pharmacological restoration of normal p53 conformation or targeted RNA-splicing inhibition enhances anti-tumor immunity and ICB efficacy. Collectively, our study has unveiled a novel function of mutp53 in establishing immunosuppressive tumor microenvironment, which provides an actionable framework for new avenue for intervention and therapy in TP53-mutated cancers.

GSE302647 A time-resolved atlas of histone modifications during mitotic entry

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Moonmoon Deb ; Natalia Y Kochanova ; Shaun Webb ; Axel Imhof ; William C Earnshaw
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Gallus gallus

Mitotic chromosome formation is essential for faithful chromosome segregation in metazoans. While condensin complexes are critical for the formation of rod-shaped mitotic chromosomes, additional mechanisms—particularly those involving phosphorylation and deacetylation of specific histone residues—have been proposed to contribute a further 2- to 4-fold reduction in mitotic chromatin volume. In this study, we employ high-resolution mass spectrometry to determine the kinetics of histone modifications in cell cultures undergoing a highly synchronous mitotic entry at 2.5-minute resolution. Our analysis reveals three different programmes of histone H3 phosphorylation on T3, S10 and S28. These modifications are consistent with methyl-phos switches regulating the association of readers with chromatin other than at promoters. Mass spectrometry and quantitative ChIP-Seq reveal that H3 T3 phosphorylation is a general marker of heterochromatin and not specifically centromeres as previously suggested. Finally, we show that histone acetylation undergoes only modest changes as rod-shaped chromosomes form during unperturbed mitotic entry. Thus, previously reported reductions in acetylation associated with chromosome formation were apparently attributable to delays in mitotic exit used as part of mitotic synchronisation protocols. The mechanism of condensin-independent chromatin compaction in mitosis remains unexplained.

GSE299896 Micropeptide UEIS attenuates cGAS-STING-type I IFN signalling to repress anti-tumour immunity

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Xingwen Wang ; Yi Zhang ; Ying Hu
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Immune checkpoint blockade (ICB) has achieved remarkable success in cancer treatment; however, enhancing its efficacy remains a significant challenge. Selectively restoring tumour-induced immune deficiency within the tumour microenvironment is considered an ideal strategy for unleashing antitumour immunity without causing severe toxicity. Here, we describe an immunoregulatory micropeptide encoded by a long non-coding RNA (lncRNA) gene identified through comprehensive bioinformatic screening, which we designate as UEIS. UEIS was found to be upregulated in tumour-associated macrophages (TAMs) and to drive macrophages toward a pro-tumorigenic phenotype, thereby inhibiting antitumour T-cell immunity. Mechanistically, the expression of UEIS is induced by cGAS-STING-type I interferon (IFN) signalling at a relatively late stage following tumoral DNA stimulation. Thus, we identify the endogenous existence of a lncRNA-encoded micropeptide and reveal its inhibitory effect on cGAS-STING-type I IFN signalling via a feedback loop in TAMs. These findings highlight UEIS as a promising therapeutic target for cancer treatment.

GSE299696 A Genome-Wide CRISPR Screen Identifies DTX4 Modulating Alveolar Macrophage Cholesterol Efflux in Pulmonary Alveolar Proteinosis [CRISPR]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Xinmei Huang ; Zimu Wang ; Jingwei Shi ; Yonglong Xiao ; Mengshu Cao ; Yingwei Zhang ; Xinye Xia
Series Type : Other
Organism : Homo sapiens

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary syndrome characterized by impaired surfactant clearance, driven by dysfunctional cholesterol efflux in alveolar macrophages (AMs). However, the molecular determinants governing AM cholesterol homeostasis remain largely elusive. Here, through a genome-wide CRISPR activation screen in foamy macrophages and bulk RNA sequencing of AMs from PAP patients, we identify Deltex E3 Ubiquitin Ligase 4 (DTX4) as a pivotal regulator of cholesterol efflux in AMs. Adeno-associated virus (AAV) -mediated silencing of DTX4 led to excessive lipid accumulation in AMs, exacerbated alveolar proteinosis, increased lung opacities on imaging, and significantly deteriorated pulmonary function in mice. Similarly, DTX4 depletion in primary AMs impaired cholesterol efflux and promoted intracellular lipid deposition. In contrast, AM-specific overexpression of DTX4 markedly alleviated lipid accumulation, mitigated alveolar proteinosis, restored lung densities on computed tomography, and rescued pulmonary function in Csf2ra-/-mice, a model of PAP. Mechanistically, DTX4 deficiency downregulated PPAR-γ expression, driving foamy AM formation. Notably, the regulatory function of DTX4 in lipid homeostasis was partially mediated by PPAR-γ but independent of its canonical E3 ubiquitin ligase activity. Collectively, our findings establish DTX4 as a central orchestrator of AM cholesterol efflux and surfactant homeostasis, positioning it as a promising therapeutic target for PAP and a potential paradigm for cholesterol dysregulation in related disorders.

GSE299693 A Genome-Wide CRISPR Screen Identifies DTX4 Modulating Alveolar Macrophage Cholesterol Efflux in Pulmonary Alveolar Proteinosis [RNA-seq II]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Xinmei Huang ; Zimu Wang ; Jingwei Shi ; Yonglong Xiao ; Mengshu Cao ; Yingwei Zhang ; Xinye Xia
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

GSE299689 A Genome-Wide CRISPR Screen Identifies DTX4 Modulating Alveolar Macrophage Cholesterol Efflux in Pulmonary Alveolar Proteinosis [RNA-seq 1]

Thu, 23 Apr 2026 00:00:00 -0400

GSE297044 SETD2 Deficiency Drives Mitochondrial DNA Leakage and Creates a Druggable Dependency on BCL-XL in Clear Cell Renal Cell Carcinoma

Thu, 23 Apr 2026 00:00:00 -0400

Contributor : Aguirre de Cubas
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

SETD2 is frequently mutated or deleted in clear cell renal cell carcinoma (ccRCC). Loss of SETD2 could create synthetic lethal dependencies that confer therapeutic vulnerabilities. Here, we demonstrated that SETD2 deficiency promotes cytoplasmic mitochondrial DNA (mtDNA) leakage, leading to basal activation of cGAS-STING inflammatory signaling and increased apoptotic priming. This inflammatory state upregulated the BH3-only protein NOXA, constrained MCL-1 function, and enforced a synthetic lethal dependency on the anti-apoptotic protein BCL-xL. Pharmacological inhibition of BCL-xL further amplified cGAS-STING signaling in SETD2-deficient cells through sublethal mitochondrial outer membrane permeabilization, resulting in increased mtDNA release and robust NOXA induction. Elevated NOXA neutralized the compensatory MCL-1-mediated survival signaling, triggering apoptosis. In contrast, SETD2 proficient ccRCC cells exhibited minimal cGAS-STING activation and failed to induce NOXA following BCL-xL inhibition, rendering them resistant. Genetic ablation of cGAS, STING, IRF3, or NOXA rescued sensitivity to BCL-xL inhibition, confirming that mtDNA-driven innate immune signaling is required for this dependency. In vivo, BCL-xL inhibition suppressed tumor growth and prolonged survival in SETD2-deficient xenograft models. Collectively, these findings establish a mechanistic link between SETD2 loss, mtDNA-driven innate immune activation, and enforced BCL-xL dependence in ccRCC, revealing a therapeutically targetable vulnerability in SETD2-deficient tumors.

GSE295557 First-in-Class CAR T Cell Therapy Selectively Eliminates Mutant Calreticulin-Driven Malignancies in a Fibrotic Niche

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Zoë C Wong ; Bethan Psaila ; Charlotte K Brierley
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Pathogenic mutations in calreticulin (mutCALR) are found in one third of patients with myeloproliferative neoplasms. All mutCALR variants yield the same protein neoepitope that forms an aberrant complex with the thrombopoietin receptor, driving oncogenic stem cell expansion, megakaryocyte hyperplasia and fibrosis. We developed a novel, first-in-class chimeric antigen receptor (CAR) T-cell therapy targeting mutCALR and evaluated efficacy in a bespoke human chimeroid model of the bone marrow. We used 10x single-cell RNA sequencing (scRNA-seq) to analyze cell composition, transcriptional differences, and cell-cell interactions.

GSE295411 Numb-Ifi204 inhibits microglial activation and the hippocampal inflammation induced by LPS

Thu, 23 Apr 2026 00:00:00 -0400

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

This study aimed to identify the mechanisms regulating microglial activation and to explore potential therapeutic targets for neuroinflammation-related cognitive dysfunction disorders. We uncover a novel role for Numb in regulating microglial activation and highlight its interaction with Ifi204 in the LPS-induced TLR4 signaling pathway. We demonstrate that Numb promotes the autophagic degradation of Ifi204, thereby inhibiting the TLR4 signaling pathway and reducing excessive inflammatory responses in microglia. Furthermore, our findings show that Numb-mediated inhibition of microglial inflammation protects hippocampal neurons from synaptic damage, morphological abnormalities, and apoptosis.

GSE294765 A skeletal muscle atlas shows neuromuscular junction adaptations to growth and atrophy

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Silvia Campanario ; Mercedes Grima-Terrén ; Megan Rommelfanger ; Stefania Dell’ Orso ; Xuesong Feng ; Ignacio Ramírez-Pardo ; Aina Calls ; Andrés Cisneros ; Kyung Dae Ko ; Esther García-Domínguez ; Davide Randazzo ; Alberto Pérez-Garcia ; Mari Carmen Gómez-Cabrera ; Tovah E Markowitz ; Benjamin Yang ; Antonio L Serrano ; Eusebio Perdiguero ; Vittorio Sartorelli ; Joan Isern ; Pura Muñoz-Cánoves
Series Type : Expression profiling by high throughput sequencing ; Other
Organism : Mus musculus

The molecular mechanisms underlying the opposing states of muscle atrophy (such as with disuse or in aging) and hypertrophy (such as with increased physical activity) are still not well-defined. Progress has been slowed by challenges in characterizing the niche heterogeneity of skeletal muscle (whereby myofibers are the most abundant) and in obtaining well-characterized samples. Here we describe: i) changes in muscle cell populations that are undergoing atrophy or hypertrophy, with complex, opposing cell transcriptional responses during each process; and ii) a remarkable remodeling of the neuromuscular junction (NMJ) domain, whereby we identify emerging new subpopulations of synaptic myonuclei (SynM) and terminal Schwann cells (tSCs) that are specifically adapted to each growth/atrophy condition. High-resolution 3D imaging and spatial transcriptomics reveal these structural and molecular adaptations at the tissue level. Critically, these changes also occur in the NMJ of both denervated and exercised human muscle. Our study lays the ground for identifying novel targets for medical, pharmacological and lifestyle interventions in aging and disease.

GSE294573 HNF4a controls growth, identity and response to KRAS inhibition in IMA.

Thu, 23 Apr 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens ; Mus musculus

This SuperSeries is composed of the SubSeries listed below.

GSE294572 HNF4a controls growth, identity and response to KRAS inhibition in IMA [ChIP- seq]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Headtlove Essel Dadzie ; Eric Snyder
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens ; Mus musculus

GSE294571 HNF4a controls growth, identity and response to KRAS inhibition in IMA [scRNA-seq]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Headtlove Essel Dadzie ; Eric L Snyder
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

GSE294570 HNF4a controls growth, identity and response to KRAS inhibition in IMA [bulk RNAseq]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Headtlove Essel Dadzie ; Eric L Snyder
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

GSE294109 Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma [scRNAseq]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Lynda Vuong ; Fengshen Kuo ; Abraham A Hakimi
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors (VEGFR-TKIs) and aPD1 combinations are effective in multiple solid tumors, particularly in clear cell renal cell carcinoma (ccRCC), due it’s characteristic pseudo-hypoxic, hyper-angiogenic state driven by biallelic VHL-loss. However, long-term durability is inferior to dual aPD1/aCTLA4 regimens, yet the mechanisms underlying these differences remain unclear. Since tumor-associated macrophages (TAMs) are implicated in therapeutic resistance, we used scRNAseq to investigate TAM evolution following VEGFR-TKI, aPD1 and combined VEGFR-TKI/aPD1 treatment in a transgenic ccRCC mouse model. We identify hypoxia-responsive SPP1+ TAMs that are absent in baseline pseudo-hypoxic tumors. This proxy of true hypoxia tracks with successful response to VEGFR-TKI/aPD1 in mouse and human on-treatment samples, reflecting treatment-induced hypoxic necrosis. Paradoxically, pretreatment hypoxia predicted worse outcomes across multiple VEGFR-TKI/aPD1 trial and real-world cohorts and extended exposure to hypoxia-inducing VEGFR-TKIs and aPD1 exacerbated metastasis in mice, highlighting the dual implications of hypoxia in ccRCC disease trajectory.

GSE294006 Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma [Spatial Transcriptomics]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Lynda Vuong ; Fengshen Kuo ; Abraham A Hakimi
Series Type : Other
Organism : Homo sapiens

GSE293952 Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma [bulk RNA-seq]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Lynda Vuong ; Fengshen Kuo ; Abraham A Hakimi
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

GSE293450 Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Lynda Vuong ; Fengshen Kuo ; Abraham A Hakimi
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

GSE291623 Glycine-modulating Slc6a20a-ASO restores NMDA receptor function in SHANK2 and SHANK3-mutant mice and cortical organoids

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Mihyun Bae ; Junyeop D Roh ; Woo-Chang Hwang ; Eunjoon Kim
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

we report 23237 singel celll transcriptomes from 5 human cortical organoids (hCOs) which was generated from H1 and maintained for 3month.

GSE290144 Thymic alveolar type II epithelial mimetic cells revealed by Runx1-deficiency [scRNA-seq]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Jun Hyung Sin ; Michael R Waterfield
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The mechanisms used to prevent autoimmune lung disease are incompletely understood. Recent studies in the thymus have identified unique populations of medullary thymic epithelial cells (mTECs) called mimetic cells that transcriptionally mimic peripheral epithelial populations. These mimetic cells have been found to have important functions in the thymus in immune tolerance and the diversity and cell types represented in this pool of cells represents an active area of investigation. Here, we utilized a mouse line with thymic specific deletion of the Runt related transcription factor 1 (Runx1) to identify a novel mimetic cell type that transcriptionally mimic alveolar type II (AT2) lung epithelial cells. Runx1 binds to genomic regions associated with epidermal growth factor receptor (EGFR) signaling suggesting a function for EGFR in regulating AT2 mTEC development.

GSE290143 Thymic alveolar type II epithelial mimetic cells revealed by Runx1-deficiency [CUT&Run]

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Jun Hyung Sin ; Michael R Waterfield
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

GSE285400 Transcriptome of Ag-specific B cells upon stimulation with soluble or particulate Ag

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Julie Zikherman ; Julianne Riggs ; Alexander J Ritter
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Primary B cells from MD4 mice have transgenic B cell receptors that recognize hen egg lysozyme (HEL). Previous studies have shown that antigens presented in different formats induce qualitatively different signaling responses in B cells. Here, we compare the transcriptomes induced by the following stimuli: LPS (10 mg/mL), particulate HEL (1pM liposomes with reduced affinity HEL-3X protein conjugated to surface at epitope density 243), soluble HEL (1mg/mL), and co-stimulation with soluble HEL and anti-CD40 (100 ng/mL).

GSE283585 Flavonoid and isoflavonoid biosynthetic gene expression is affected by MYB36 transcription factor deficiency in Lotus japonicus

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : María D Monje-Rueda ; Margarita García-Calderón
Series Type : Expression profiling by high throughput sequencing
Organism : Lotus japonicus

This SuperSeries is composed of the SubSeries listed below.

GSE264442 Unleashed condensation by recurrent mutations of an epigenetic regulator promotes cancer

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Yansu Song ; Yi Hao ; Maria Latac ; Marta Cykowiak ; Hao Jiang
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The pathological mechanisms and significance for the prevalent mutation hotspots in disordered protein regions are poorly understood. ASXL1 is an obligate co-factor for BAP1 in H2AK119 deubiquitination. ASXL1 mutations are very frequent in myeloid malignancies, and are mostly C-terminal truncating mutations concentrated in a specific disordered region of ASXL1. ASXL1 truncations are gain-of-function mutations that promote myeloid malignancies, but the underlying mechanisms remain poorly understood. Here we show that the frequently truncated mutants of ASXL1 possess an intrinsic property of forming phase-separated biomolecular condensates, and this property is normally suppressed by the frequently deleted regions. A disease-mutant of the endogenous ASXL1 in leukemia cells forms dynamic nuclear co-condensates with other endogenous factors important for gene activation. While the ASXL1 disease-mutant can greatly enhance H2A deubiquitination activity of BAP1 in cells and in a purified system, enhance the growth of myeloid leukemia cell growth, and promote hematopoietic colony formation and leukemogenesis in a mouse transplant model by turning on myeloid leukemogenic transcriptional programs, substitution of residues important for condensation disrupted or impaired these abilities, suggesting that the condensation property is crucially important for the ASXL1 mutants in promoting cancer. Moreover, we discover that the conserved negative charges in the highly disordered and frequently deleted region on ASXL1 suppress the condensation of the wild type ASXL1. Charge-neutralizing mutations in this region restores condensation of the full-length ASXL1, and renders the full-length protein capable of promoting leukemogenesis-associated activity and gene expression. Biochemical, biophysical, and simulation analyses suggest the intramolecular interactions normally mask the N-terminal region in engaging intermolecular interactions required for phase separation, and disease truncations escape from the regulatory interactions and unleash the phase separation property to form nuclear hubs to promote expression of tumorigenic gene programs. Finally, by showing a striking correlation of the mutation frequencies with the condensation properties and leukemogenesis activity for a series of human patient mutations, we suggest that dysregulation of condensation is a likely a central mechanism for ASXL1 mutations in promoting myeloid malignancies. This may also be an overlooked mechanism for the prevalent hotspot disease mutations in the disordered proteomes.

GSE247763 Tissue-specific VEGF-D overexpression induces lymphangiogenesis and heterotopic bone resorption

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Neda Vishlaghi ; Benjamin Levi ; Michael Dellinger
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Heterotopic ossification (HO) is a pathological process that commonly occurs after musculoskeletal injury and is characterized by the formation of bone in non-skeletal tissues. Despite advances in research, no effective treatments are available to promote the resorption of heterotopic bone in patients suffering from HO. Lymphatic vessels are associated with the destruction of bone in rare diseases such as Gorham-Stout disease. However, the effect of lymphatic vessels on HO was previously unknown. Here, we use transgenic mice to determine whether targeted expression of the lymphatic growth factor VEGF-D can promote the therapeutic resorption of bone in a mouse model of HO. We show that control mice lack lymphatic vessels in heterotopic bone. In contrast, Vegfd-overexpressing (Vegfd-OE) mice develop lymphatic vessels in heterotopic bone and form significantly less heterotopic bone than control mice. Additionally, we demonstrate that VEGF-D promotes the resorption of established heterotopic bone. Mechanistically, we show that the transition of myeloid cells to osteoclasts and osteoclast-mediated bone resorption are enhanced in Vegfd-OE mice. Our findings suggest that site-directed lymphangiogenesis could be an effective strategy to break down heterotopic bone in HO.

GSE218624 Single cell RNA-sequencing of the preoptic area of hypothalamus from sleep deprivation and rebound sleep mice

Thu, 23 Apr 2026 00:00:00 -0400

Contributors : Huateng Cao ; Zhe Zhang
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Using single-cell transcriptomics to search for hypothalamic neurons representing and controllling sleep pressure, we identified a group of neurons expressing Gpr139 in the preoptic area (POA) selectively activated during rebound sleep (RS) after sleep deprivation (SD).