GEO 数据集

主题由标题与摘要自动归类；样本量为数据集标注之和，SuperSeries 可能与其 SubSeries 重复计算。

• Endogenous variability in transcription factor concentrations shapes their genome-wide occupancy [ATAC-seq]
  GSE308326Mus musculus8 个样本2026-10-27

  The control of transcription factor (TF) concentrations is crucial for the precise regulation of gene expression and cell fate decisions during development. Yet, TF concentrations can display substantial temporal fluctuations and intercellular variations. How TF levels quantitatively shape genome-wide occupancy patterns remains largely unexplored. Here, we systematically investigate how physiological fluctuations in the concentrations of the pluripotency TFs OCT4, SOX2, and NANOG impact their genomic binding profiles in mouse embryonic stem cells. We uncover distinct concentration-dependent binding behaviors for each TF. NANOG occupancy increased monotonously with its concentration, even though a common set of regions made accessible by OCT4 and SOX2 were highly and uniformly bound at all NANOG concentrations. In contrast, SOX2 occupancy does not increase with its concentrations, while OCT4 displayed an intermediate behavior. Our results challenge the notion that TF binding follows simple mass-action dynamics and reveal a core set of pluripotency regions that are bound by all three TFs at all TF concentrations, revealing how pluripotency can be maintained despite marked fluctuations in core pluripotency TFs.
• Single Cell multi-omics identifies VEGFA-mediated angiogenesis results in relapse in Sonic Hedgehog Medulloblastoma [Visium]
  GSE287107Homo sapiens6 个样本2026-10-27

  Relapse in Sonic Hegdehog Medulloblastoma (SHH-MB) a common pediatric brain tumor, remain a significant clinical challenge due to its poor prognosis and limited therapeutic intervention. Understanding the underlying molecular mechanisms driving relapse is critical for developing targeted interventions. Here, we utilize single-cell multi-omics, combining single-nucleus RNA sequencing (snRNA-seq), single-nucleus ATAC sequencing (snATAC-seq), and spatial omics to comprehensively characterize the cellular landscape and regulatory networks associated with SHH medulloblastoma relapse. Our integrative analysis identifies distinct GCP population enriched with angiogenic activity characterized high expression of Vascular Endothelial Growth Factor A (VEGFA) regulated by the transcription factor HIF1A. Notably, we find that VEGFA-mediated angiogenesis is a critical driver of tumor recurrence, promoting a microenvironment that supports tumor revascularization and growth in the endothelial cells. Furthermore, we uncover potential therapeutic targets within the VEGFA signaling axis that could disrupt angiogenesis and reduce relapse rates. Our findings provide new insights into the molecular and cellular dynamics of SHH medulloblastoma relapse and highlight VEGFA as a key mediator of angiogenesis-driven recurrence, offering a promising avenue for therapeutic intervention.

  单细胞空间转录组多组学
• Next Generation Sequencing Facilitates Quantitative Analysis of Transcriptome profile in ileum tissue from mice infected with C. parvum at days 3 post-infection.
  GSE272799Mus musculus6 个样本2026-10-27

  Cryptosporidium spp., an apicomplexan protozoan, is one of the most common pathogens responsible for moderate-to-severe diarrhea in children under 2-year-old. Metabolic dysregulation in host following Cryptosporidium infection remains obscure. In the current study, we analyzed the transcriptome of ileal epithelium from mice infected with C. parvum to identify potential genes involved in metabolic reprogramming. Total RNA was collected for the genome-wide analysis, for sequencing using BGISEQ-500 platform.
• Discovery of a novel inhibitor of macropinocytosis with antiviral activity
  GSE246407Homo sapiens6 个样本2026-10-27

  Several viruses hijack various forms of endocytosis in order to infect animal cells. Here, we report the discovery of a new molecule with antiviral properties, that we named virolin, which limits viral entry by macropinocitosis. The identification of virolin derives from a chemical screen using High-Throughput Microscopy, where we identified new chemical entities capable of preventing infection with a pseudotype virus expressing the spike (S) protein from SARS-CoV-2. Subsequent experiments confirmed the capacity of virolin to limit infection by actual SARS-CoV-2, as well as by additional viruses, such as Monkeypox or TBEV. Mechanistic analyses revealed that the compound inhibited macropinocytosis, limiting this entry route for the viruses. Importantly, virolin has no significant toxicity to host cells. In summary, we present a new molecule that inhibits viral entry via the endocytic route, offering a new alternative to prevent viral infection.
• Next Generation Sequencing Facilitates Quantitative Analysis of Transcriptome profile in liver tissue from mice infected with C. parvum at days 3 post-infection.
  GSE234579Mus musculus6 个样本2026-10-27

  Cryptosporidium spp., an apicomplexan protozoan, is one of the most common pathogens responsible for moderate-to-severe diarrhea in children under 2-year-old. Metabolic dysregulation in host following Cryptosporidium infection remains obscure. In the current study, we analyzed the transcriptome of liver tissue from mice infected with C. parvum to identify potential genes involved in metabolic reprogramming in the liver. Total RNA was collected for the genome-wide analysis, for sequencing using BGISEQ-500 platform.
• Improvement of monoclonal antibody therapy against cancer through engineering stem cell-derived CD16-enhanced universal NKT cells (TCR)
  GSE352161Homo sapiens1 个样本2026-10-26

  Monoclonal antibody (mAb)-based therapies have revolutionized cancer treatment; however, their clinical efficacy is often limited by insufficient antibody-dependent cellular cytotoxicity (ADCC), tumor antigen escape, and an immunosuppressive tumor microenvironment (TME). To overcome these limitations, we developed an allogeneic stem cell-derived invariant natural killer T (NKT) cell platform engineered to express a high-affinity non-cleavable CD16 receptor (CD16HSC-NKT) for broad enhancement of mAb-based immunotherapy. Using a clinically guided differentiation platform, we generated highly pure and scalable CD16HSC-NKT cells exhibiting robust expression of NK receptors, potent cytotoxic machinery, and a Th1-biased cytokine profile. CD16HSC-NKT cells demonstrated potent intrinsic antitumor activity and potently enhanced the efficacy of multiple therapeutic antibodies, including Trastuzumab, Tafasitamab, Rituximab, Daratumumab, and Cusatuzumab, across diverse hematologic and solid tumor models. In vivo, combination therapy induced durable tumor eradication and prolonged survival in xenograft models, outperforming the clinically approved antibody-drug conjugate trastuzumab deruxtecan. Mechanistically, therapeutic antibodies promoted the expansion, persistence, and activation of CD16HSC-NKT cells within tumors. Importantly, CD16HSC-NKT uniquely remodeled the TME by selectively depleting CD1d-expressing tumor-associated macrophages and myeloid-derived suppressor cells. CD16HSC-NKT cells also exhibited minimal alloreactivity, no graft-versus-host disease, and no detectable systemic toxicity. Collectively, these findings establish CD16HSC-NKT cells as a safe, off-the-shelf cellular platform capable of broadly enhancing monoclonal antibody therapy through sustained ADCC, multimodal tumor targeting, and TME remodeling.
• BAP1 safeguards double-strand DNA break repair by limiting DNA end resection
  GSE351902Homo sapiens6 个样本2026-10-26

  The tumor suppressor BAP1 is frequently mutated in uveal melanoma and has been linked to homologous recombination (HR), yet how it influences DNA double-strand break (DSB) repair pathway choice remains unclear. Here, we identify BAP1 as a critical regulator that restricts DNA end resection to preserve non-homologous end-joining (NHEJ) capacity. Loss of BAP1 leads to aberrant accumulation of H2AK119 ubiquitination at DSBs, driving unscheduled resection in G1-phase cells and impairing recruitment of the anti-resection factor 53BP1. Co-depletion of the resection initiator CtIP restores NHEJ efficiency in BAP1-depleted cells, and pharmacological suppression of H2AK119 ubiquitination reverses these defects, placing unscheduled resection causally upstream of the end-joining failure. RNA sequencing and genome-wide H2AK119ub profiling show that neither the expression of NHEJ and HR genes nor the H2AK119ub landscape at their promoters is appreciably altered by BAP1 loss, supporting a role of altered H2AK119ub at the DSBs. These findings indicate that BAP1 safeguards DSB repair fidelity by preventing hyper-resection, thereby maintaining NHEJ competence. Consistent with this role, BAP1-depleted cells accumulate micronuclei, and BAP1 loss is associated with genomic instability in human uveal melanoma. Together, our results uncover a mechanism by which chromatin regulation constrains resection to coordinate repair pathway utilization.
• Molecular mapping of developing synovial fibroblasts in the TMJ reveals the crucial role of mechanical force in cavitation
  GSE351686Homo sapiens3 个样本2026-10-26

  The temporomandibular joint is formed from neural crest-derived mesenchyme with delayed development, distinct from other mesodermal derived majority synovial joints. Here, we perfomed spatial transcriptomics on human embryo samples at the initiation and cavitation stage from 9th , 10th and 11th post-conception weeks (PCW) to profile cellualr identity, singalling activity, extracellular matrix dynamics and ligand-receptor interactions during TMJ development. Our analysis has indicated the significant roles of synoival fibroblasts during the cavitation stage in the developing TMJ.

  空间转录组
• Novel WRN Exon 10 Skipping Mutation Triggers Progerin Accumulation and Premature Aging
  GSE351663Mus musculus6 个样本2026-10-26

  Werner Syndrome (WS) is an autosomal recessive disorder characterized by premature aging and increased susceptibility to various age-related diseases, predominantly caused by mutations in the WRN gene. This study investigated a Chinese patient with WS and partial lipoatrophic diabetes mellitus, aiming to identify a novel pathogenic variant in the WRN gene. High-throughput sequencing was conducted on genomic DNA from a blood sample. The identified homozygous variant (WRN_intron9 c.1270-1G>C) was confirmed, and its pathogenicity was assessed through in silico predictions, structural modeling, and cell function assays. The variant's effect on exon skipping was analyzed, and cellular assays were performed to validate the induced phenotype. The study identifies a novel WRN variant as a potential pathogenic factor in the patient. Simulations predict that the WRN_intron9 c.1270-1G>C mutation triggers exon 10 skipping, deleting one of the two highly homologous peptide regions encoded by exon 10 and exon 11 respectively. Cellular assays confirm senescent phenotype induction and human progerin accumulation, leading to premature cellular senescence.

  计算与 AI
• IGF1R-derived glycolysis maintains primordial follicle survival in neonatal mouse ovaries
  GSE351522Mus musculus6 个样本2026-10-26

  In mammals, the primordial follicle pool is essential for sustaining female fertility. In the present study, insulin-like growth factor 1 (Igf1) was found to be markedly low in neonatal mouse ovaries relative to its dramatic expression in the liver, whereas Igf2 exhibited high expression levels in both neonatal ovarian and hepatic tissues. IGF1 receptor (IGF1R) was mainly localized in the pre-granulosa cells and oocytes of mouse primordial follicles. IGF1R inhibitors ADW-742 and AEW-541 significantly decreased the number of primordial and growing follicles in cultured neonatal mouse ovaries. Further studies revealed that ADW-742 decreased glycolysis-related gene expression and amino acid levels in neonatal mouse ovaries, and caused mitophagy in pre-granulosa cells and autophagic flux blockade in oocytes of primordial follicles. Enhanced glycolysis by short-term pyruvate-free treatment and/or signal transducer and activator of transcription 3 (STAT3) activator colivelin increased amino acid levels and partially reversed ADW-742-induced mitophagy and follicle apoptosis. Finally, ADW-742 also induced autophagy in human oocytes. Thus, IGF/IGF1R maintains the survival of primordial follicles through glycolysis. These findings offer novel insights into the mechanisms underlying the maintenance of female mammalian fertility.
• RNA Polymerase II Dynamics in Antiviral NK Cell Responses [Pol II ChIP-Seq]
  GSE351024Mus musculus2 个样本2026-10-26

  Natural killer (NK) cells are innate lymphocytes that uniquely exhibit both innate and adaptive responses towards certain pathogens. During cytomegalovirus (CMV) infection, antigen-specific NK cells will generate a long-lived pool of memory cells with enhanced responses to secondary infection. The underlying molecular mechanisms that regulate early innate effector functions and delayed adaptive proliferation followed by longevity during antiviral NK cell differentiation remain to be fully understood. Here, we investigated the dynamics of serine-5 phosphorylated RNA Polymerase II (Pol IIS5P) occupancy in NK cells ex vivo during mouse CMV (MCMV) infection. During the initial NK cell antiviral response, Pol IIS5P occupancy increased broadly across the genome, at both upregulated and downregulated genes relative to NK cells at rest. NK cells across response states showed distinct enrichment of Pol IIS5P at transcriptional start sites (TSS) versus non-promoter regions with select genes maintaining Pol IIS5P occupancy throughout MCMV infection to the memory phase. Thus, our findings illustrate the dynamic Pol IIS5P genomic occupancy in NK cells during antiviral immunity.
• METTL16-associated RNAs in human Jurkat cells profiled by RIP-seq
  GSE347246Homo sapiens4 个样本2026-10-26

  This study aimed to identify RNAs associated with METTL16 in human Jurkat cells using RNA immunoprecipitation followed by high-throughput sequencing (RIP-seq). METTL16-immunoprecipitated RNA and matched input RNA were profiled from two untreated biological replicates. Gene-level read counts were generated to assess RNA enrichment in METTL16 immunoprecipitates relative to input controls.
• Recordanelles for transcriptome-wide single-cell RNA recording in human cells [dataset_4 scRNA-seq]
  GSE344737Homo sapiens2 个样本2026-10-26

  Transcriptomic measurement technologies provide powerful approaches to understand biology but are limited to providing either a high-resolution snapshot at a moment in time or a low-resolution history of transcription constrained to a few genes over a narrow time range. Here, we introduce the “recordanelle”, a single-component synthetic organelle capable of recording the transcriptome in human cells. Recordanelles are composed of a mitochondrial membrane anchor, a condensate assembler and a poly-A-binding protein. We demonstrate that the recordanelle can be engineered to recruit engineered RNAs or a sampling of up to 90% of all endogenous mRNAs and protect them over several days. We further show that transient and dynamic transcriptional responses resulting from inducible promoters or interferon signaling are preserved throughout time within the recordanelle at the single-cell level. This work provides a non-disruptive and unbiased transcriptome-wide single-cell RNA recording technology to enable a deeper understanding of biology.

  单细胞
• CCL11 regulates microglial responses in aged mice following ICH.
  GSE344735Mus musculus6 个样本2026-10-26

  CCL11 level increases in circulation with age, with the ability to penetrate the brain, where it attenuates homeostatic functions. Microglia (MG) are essential brain tissue macrophages, and are critical for improved ICH outcomes. To study the effect of systemic-neutralization of CCL11 in aged mice, particularly on MG gene expression changes following ICH injury, we performed RNA-sequencing of MG collected after experimental ICH in a mouse blood injection model. We intraperitoneally administered an anti-CCL11 antibody to aged male mice prior to ICH, isolated MG from the ipsilateral hemisphere, and used the MG for bulk RNA-sequencing analysis. We found that sequestration of CCL11 in the circulation of aged mice prior to ICH upregulates the expression of microglial genes linked to pro-phagocytic, anti-oxidative, and anti-inflammatory signaling.
• TNFR2 agonism increases tissue and effector Treg cells
  GSE344625Mus musculus2 个样本2026-10-26

  Autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus are driven by chronic inflammation and tissue damage. Regulatory T (Treg) cells are critical for maintaining immune tolerance, yet their therapeutic use is limited by stability and tissue homing. Here, we demonstrate that agonism of tumor necrosis factor receptor 2 (TNFR2) increases effector and tissue-competent Treg cell progenitors in mice and humans. Single-cell RNA sequencing reveals that TNFR2 is highly expressed on early and late non-lymphoid tissue Treg cell precursors, with expression strongly correlated with the BATF-driven tissue Treg cell transcriptional program. In vivo, a single dose of TNFR2 agonist promotes the clonal commitment of Treg cells to effector and tissue lineage, increasing tissue Treg cell populations in lymphoid and peripheral tissues. This increase is associated with enhanced suppressive function, epigenetic stability (preserved FOXP3 CNS2 demethylation), and resistance to inflammatory conversion. In murine models of skin inflammation and experimental autoimmune encephalomyelitis, TNFR2 agonism ameliorates disease severity in a dose-dependent manner. Critically, in human Treg cells, TNFR2 agonism induces elements of the tissue residency transcriptional program—including upregulation of LAYN, CCR8, CCR4 and TIGIT—while maintaining lineage stability. These findings establish TNFR2 signaling as a central driver of effector and tissue Treg cell differentiation and position TNFR2 agonism as a transformative strategy for generating stable, tissue-competent effector Treg cells as a promising immunomodulatory therapy for autoimmune and inflammatory diseases.

  单细胞
• Transcriptomic profiling of C17orf58 knockdown in Jurkat T cells
  GSE343757Homo sapiens9 个样本2026-10-26

  C17orf58 is a poorly characterized gene implicated in the survival and proliferation of T-cell malignancies. To characterize transcriptional changes associated with C17orf58 depletion, RNA sequencing was performed in Jurkat T cells following lentiviral transduction with shRNAs targeting C17orf58. Two independent C17orf58-targeting shRNA constructs were evaluated, with scrambled shRNA and luciferase-targeting shRNA serving as negative controls. RNA was collected 72 hours after lentiviral transduction and subjected to RNA sequencing to identify gene-expression changes and molecular pathways associated with C17orf58 depletion.

  扰动筛选
• Attenuation of DOK3 re-programs tumor-associated macrophages to enhance anti-PD-1-mediated cancer immunotherapy
  GSE343606Homo sapiens1 个样本2026-10-26

  Downstream of Kinase 3 (DOK3) is an adaptor protein that binds and modulates Caspase recruitment domain-containing protein 9 (CARD9) signaling but the role for DOK3 during tumor immune escape remains unclear. Here, we revealed immunosuppressive Osteopontin (SPP1+) tumor-associated macrophages (TAMs) to highly express DOK3 while DOK3low/neg TAMs express CARD9 and T cell-homing chemokines within the tumor microenvironment (TME). Interestingly, Dok3-/- mice showed decreased tumor growth and improved response to anti-PD-1 therapy. While DOK3 is constitutively expressed by macrophages, blocking its interaction with CARD9 enhances JNK signaling to reprogram TAMs for improved homing and activation of T cells. Further spatial studies clarified the localization of DOK3high TAMs within the TME and an association of DOK3 expression with progressive disease in an ongoing Phase II study of Lenvatinib/Pembrolizumab in recurrent clear cell gynecological carcinomas. Overall, targeting DOK3-CARD9 axis may represent a new avenue to overcome resistance in cancer immunotherapy by driving the emergence of favorable response-associated TAM states.

  空间转录组
• The antioxidant (+)-Catechin reduces inflammation and promotes a stable plaque phenotype in female LDL receptor deficient mice fed a high-fat diet via anti Inflammatory and smooth muscle cell regulatory pathways [human]
  GSE343575Homo sapiens6 个样本2026-10-26

  Nutraceuticals such as (+)-Catechin are emerging as promising agents for the prevention and treatment of atherosclerotic cardiovascular disease. A large prospective study of 34,492 participants previously demonstrated an inverse association between (+)-Catechin intake and risk for coronary heart disease. Our recent work further showed that (+)-Catechin inhibits several atherosclerosis related processes in vitro, induces beneficial metabolic changes in male C57BL/6J mice fed a high fat diet (HFD), and reduces plaque burden and inflammation in male low-density lipoprotein (LDL) receptor deficient (LDLr / ) mice fed a HFD. Given known sex specific differences in atherosclerosis, it is essential to extend these investigations to female mice. The objective of this study was therefore to investigate the effects of (+)-Catechin in female LDLr / mice in vivo. (+)-Catechin lowered plasma cholesterol levels, reduced circulating T cell populations, and increased several beneficial short chain fatty acids in both the plasma and the faeces. It also decreased plaque size, lipid content, macrophage accumulation, and CD3⁺ T cell infiltration in the aortic root, while enhancing markers of plaque stability. RNA sequencing (RNA seq) of the thoracic aorta revealed modulation of key pathways involved in inflammatory signalling, hypertension and immune responses. Complementary studies in human aortic smooth muscle cells demonstrated that (+)-Catechin attenuated macropinocytosis and oxidised LDL uptake, processes linked to plaque progression, without promoting calcification. RNA seq identified several genes and pathways consistent with the compound’s anti atherogenic and plaque stabilising actions. Collectively, these findings provide new mechanistic insights into the beneficial cardiovascular effects of (+)-Catechin in female mice and support further evaluation of this flavanol in human clinical trials.
• The antioxidant (+)-Catechin reduces inflammation and promotes a stable plaque phenotype in female LDL receptor deficient mice fed a high-fat diet via anti Inflammatory and smooth muscle cell regulatory pathways
  GSE342632Mus musculus6 个样本2026-10-26

  Nutraceuticals such as (+)-Catechin are emerging as promising agents for the prevention and treatment of atherosclerotic cardiovascular disease. A large prospective study of 34,492 participants previously demonstrated an inverse association between (+)-Catechin intake and risk for coronary heart disease. Our recent work further showed that (+)-Catechin inhibits several atherosclerosis related processes in vitro, induces beneficial metabolic changes in male C57BL/6J mice fed a high fat diet (HFD), and reduces plaque burden and inflammation in male low-density lipoprotein (LDL) receptor deficient (LDLr / ) mice fed a HFD. Given known sex specific differences in atherosclerosis, it is essential to extend these investigations to female mice. The objective of this study was therefore to investigate the effects of (+)-Catechin in female LDLr / mice in vivo. (+)-Catechin lowered plasma cholesterol levels, reduced circulating T cell populations, and increased several beneficial short chain fatty acids in both the plasma and the faeces. It also decreased plaque size, lipid content, macrophage accumulation, and CD3⁺ T cell infiltration in the aortic root, while enhancing markers of plaque stability. RNA sequencing (RNA seq) of the thoracic aorta revealed modulation of key pathways involved in inflammatory signalling, hypertension and immune responses. Complementary studies in human aortic smooth muscle cells demonstrated that (+)-Catechin attenuated macropinocytosis and oxidised LDL uptake, processes linked to plaque progression, without promoting calcification. RNA seq identified several genes and pathways consistent with the compound’s anti atherogenic and plaque stabilising actions. Collectively, these findings provide new mechanistic insights into the beneficial cardiovascular effects of (+)-Catechin in female mice and support further evaluation of this flavanol in human clinical trials.
• T cell Mechanomemory Takes Training
  GSE341175Homo sapiens8 个样本2026-10-26

  Biomaterials provide a powerful tool for directing the function of T cells, mediators of adaptive immunity and cellular immunotherapy. As an intriguing facet of biomaterial design, modulating the mechanical stiffness of biomaterials provides control over T cell activation, optimizing expansion through a parameter that is orthogonal to and can be combined with other approaches. A key question is whether mechanosensing is limited to immediate impacts on cell function or includes long-lasting imprints on cell function. This report demonstrates such a mechanomemory in the context of expansion of T cells for immunotherapy; populations activated on mechanically soft surfaces exhibit an extended proliferative phase for multiple generations following removal from the substrate. Using media manipulation, this report shows that mechanomemory is mediated by both intrinsic, epigenetic changes and extrinsic factors associated with cell-cell signaling. Moreover, the impact of extrinsic factors decreases over the course of expansion. The development and solidification of mechanomemory in T cells over multiple cell divisions provides new design rules for optimization and insights into how these agents interpret mechanically complex microenvironments.
• Attenuation of DOK3 re-programs tumor-associated macrophages to enhance anti-PD-1-mediated cancer immunotherapy [scRNA-seq]
  GSE341136Homo sapiens6 个样本2026-10-26

  Downstream of Kinase 3 (DOK3) is an adaptor protein that binds and modulates Caspase recruitment domain-containing protein 9 (CARD9) signaling but the role for DOK3 during tumor immune escape remains unclear. Here, we revealed immunosuppressive Osteopontin (SPP1+) tumor-associated macrophages (TAMs) to highly express DOK3 while DOK3low/neg TAMs express CARD9 and T cell-homing chemokines within the tumor microenvironment (TME). Interestingly, Dok3-/- mice showed decreased tumor growth and improved response to anti-PD-1 therapy. While DOK3 is constitutively expressed by macrophages, blocking its interaction with CARD9 enhances JNK signaling to reprogram TAMs for improved homing and activation of T cells. Further spatial studies clarified the localization of DOK3high TAMs within the TME and an association of DOK3 expression with progressive disease in an ongoing Phase II study of Lenvatinib/Pembrolizumab in recurrent clear cell gynecological carcinomas. Overall, targeting DOK3-CARD9 axis may represent a new avenue to overcome resistance in cancer immunotherapy by driving the emergence of favorable response-associated TAM states.

  单细胞空间转录组
• Single-cell RNA sequencing of visceral adipose tissue CD45+ immune cells from saline- and recombinant ANXA8 (rANXA8)-treated diet-induced obese mice
  GSE341132Mus musculus2 个样本2026-10-26

  Visceral obesity drives adipose tissue macrophage (ATM) inflammation. To resolve adipose immune-cell heterogeneity beyond the M1/M2 framework and define how the visceral adipose-derived adipokine Annexin A8 (ANXA8) remodels the immune landscape, we performed droplet-based single-cell RNA sequencing (MobiCube 3' RNA) of CD45+ immune cells isolated from the stromal vascular fraction (SVF) of visceral (gonadal) adipose tissue of diet-induced obese male C57BL/6 mice treated with either saline (vehicle) or recombinant ANXA8 protein (rANXA8, 2.5 mg/kg/day, i.p., 4 weeks). Unbiased clustering resolved multiple macrophage subpopulations (perivascular [PVM], lipid-associated [LAM] and nerve-associated [NAM] macrophages) alongside monocytes, dendritic cells and other immune and stromal cells. rANXA8 treatment reduced pro-inflammatory and increased anti-inflammatory/homeostatic transcriptional programs across macrophage subpopulations, indicating that ANXA8 reprograms the adipose macrophage landscape toward a less inflammatory, more homeostatic state.

  单细胞
• Non-enzymatic functions of CBP/EP300 are harnessed by gene-targeted inducers of proximity [RNA-seq]
  GSE337925Homo sapiens8 个样本2026-10-26

  Friedreich’s ataxia (FRDA) is a rare neurodegenerative disease caused by an expansion of GAA-trinucleotide repeats within the frataxin (FXN) gene. These GAA repeat expansions are enriched in repressive chromatin marks that accompany near complete silencing of the gene. Restoring FXN expression is thus a curative therapeutic goal. Here, we report the development of bifunctional synthetic gene regulators (SynGR-KATs) that recruit lysine acetyl transferases CBP/KAT3A and EP300/KAT3B to GAA repeat expansions. The GAA-targeted enzymes install transcriptionally conducive acetyl marks on proximal chromatin and restore FXN expression. Proximity-induced pharmacology of CBP/EP300 focuses solely on the enzymatic activity of these multi-domain proteins; however, we find that the non-enzymatic protein scaffolding functions contribute in equal measure to FXN expression. Highlighting the importance of protein scaffolding, co-treatment of patient-derived FRDA cells with BRD4/BET-binding SynGRs (SynGR-BETs) along with SynGR-KATs enhanced FXN expression beyond what can be achieved by either class of molecules on their own. Thus, SynGR-KATs serve as invaluable probes of transcriptional regulation while also providing a new path to therapeutic restoration of FXN expression.
• Oxidative Stress Potentiates a STAT1–APOL1 Feedforward Loop and Governs Disease Severity in APOL1-Mediated Kidney Disease [Xenium]
  GSE334605Mus musculus2 个样本2026-10-26

  Introduction: Apolipoprotein L1 (APOL1) risk variants (G1 and G2) confer immunity against Trypanosoma infection but markedly increase susceptibility to progressive kidney disease. However, only a subset of biallelic risk-variant carriers develops disease progression, distinct from murine models. Here, we evaluated molecular drivers of progressive disease using a model that reflected the low human disease penetrance. Methods: To investigate the heterogeneity of APOL1-mediated kidney disease, we generated novel APOL1 bacterial artificial chromosome transgenic mice with doxycycline-inducible systemic IFNγ expression (G0- or G1-IFNγ mice). Single-cell spatial transcriptomics via 10x Genomics Xenium In Situ platform was performed.

  单细胞空间转录组
• The nail mesenchyme creates a regeneration-specific ligand environment that orchestrates mammalian regeneration versus fibrotic wound healing [scRNA-seq]
  GSE326786Mus musculus4 个样本2026-10-26

  The adult digit tip is one of the few privileged mammalian tissues that can regenerate. Here, we have asked why this is so. We show, using single cell spatial transcriptomics and genetic mouse models that regeneration requires the nail organ and associated inductive nail mesenchyme, and that in their absence the digit tip undergoes fibrotic wound-healing. We further show the nail organ/mesenchyme orchestrates a highly-organized regenerative response where mesenchymal cells are reprogrammed to a blastema state and re-epithelialization is enhanced. It does this by creating a regeneration-specific ligand environment that is absent in the nonregenerative condition and that includes multiple BMPs. Loss of downstream BMP signaling by genetic deletion of Smad4 in all mesenchymal cells or specifically in the nail mesenchyme inhibits multiple aspects of the regenerative response, including expression of regeneration-specific ligands. Thus, the nail mesenchyme creates a BMP-rich local ligand environment that reprograms mesenchymal cells to a blastema state and promotes tissue regeneration versus fibrotic wound-healing, findings with implications for tissue repair and anti-fibrosis strategies.

  单细胞空间转录组
• Overlapping MHC class I/II epitopes program monocyte-derived dendritic cells toward a cDC1-like state via mTORC1 pathway inhibition [scRNA-seq]
  GSE325592Mus musculus6 个样本2026-10-26

  Viral infection polarizes monocyte derived dendritic cells (moDC) to initiate type 1 immune responses. The availability of homologous (overlapping) MHC class I and II epitopes, an occurrence associated with viral infection, significantly enhances this process; however, the underlying mechanism(s) remain unclear. We demonstrate that moDC loaded with homologous MHC epitopes acquire a cDC1-like phenotype in a process governed by mTORC1. mTORC1 pathway inhibition among cDC1-like cells leads to NF-B-mediated expression of IL-12 and other type I immune polarizing genes. The cDC1-like signature was also significantly enhanced in clinical moDC vaccine products for glioblastoma and PDAC made through methodologies that enforced class I and II antigenic homology. Collectively, these findings reveal a novel mechanism of immune governance that may also be exploited in cancer immunotherapy.

  单细胞
• NFIC condensates partition NMNAT1 to limit nuclear NAD+ synthesis and promote cellular senescence
  GSE317403Homo sapiens6 个样本2026-10-26

  In this study, two groups of human-derived U2OS cells were subjected to transcriptome comparative analysis, including the control group (ctrl) and the gene knockout group (KO), with three biological replicates set for each group. Using eukaryotic UID-mRNA sequencing technology, the characteristics of transcriptomic changes in cells after gene knockout were systematically identified and analyzed.
• A Novel Syngeneic Mouse Model of Metastatic Hormone-Sensitive Prostate Cancer Provides a Platform for Studying Combination Immunotherapy II
  GSE312299Mus musculus2 个样本2026-10-26

  Immunocompetent, hormone-sensitive models of metastatic prostate adenocarcinoma remain limited. We established PL051, a syngeneic luciferase-labeled cell line derived from a Pten^pc-/-;Lkb1^pc-/- (PTEN/LKB1-deficient) mouse background, and profiled its genome and transcriptome alongside tumors from the progenitor GEMM. Whole-exome sequencing (WES) of matched samples shows that PL051 is genetically near-identical to the primary tumor: we detected only one high-confidence somatic coding variant, and copy-number alterations (CNAs) were minimal, with <20% of the captured exome altered. CNAs were predominantly focal (~1–3 kb) and gene-sparse. To map androgen-receptor (AR) signaling at the transcript level, we performed RNA-seq on PL051 following vehicle, dihydrotestosterone (DHT), enzalutamide, and the DHT+enzalutamide combination. The dataset captures agonist-induced AR target activation and antagonist-associated transcriptional shifts (including cell-cycle effects), providing a resource to interrogate AR pathway dynamics in an immune-competent, metastatic context. Together, these data benchmark PL051 as a faithful, transplantable derivative of the GEMM and supply harmonized genomic and transcriptomic profiles suitable for comparative and mechanistic analyses.
• IGF2 regulates postnatal adipocyte progenitor proliferation and differentiation
  GSE309372Mus musculus2 个样本2026-10-26

  Functional adipose tissue is critical to metabolic homeostasis, the development of which occurs through a combination of hyperplastic expansion of adipocyte number and hypertrophic adipocyte growth. The relative contribution of these two fundamental growth mechanisms shifts in favor of hypertrophy with advancing age, suggesting stage specific regulatory mechanisms. Here, we merged stable isotope tracer measurements of adipogenesis with cell cycle analyses of primary murine adipocyte progenitor (AP) cells and defined an early hyperplastic-to-hypertrophic growth switch in the first 2 postnatal weeks. Through integration of bulk and single cell transcriptomics, we identified insulin-like growth factor 2 (IGF2) as lead candidate regulator, the expression of which was largely limited to the early post-natal period in AP cells. Using mouse models of AP-targeted Igf2 genetic manipulation, loss of function impaired postnatal AP proliferation and adipose growth leading to adipose dysfunction that persisted into adulthood and with diet-induced obesity. Conversely, AP-targeted gain of Igf2 preserved systemic metabolic function despite increased diet-induced weight gain and adiposity. This study establishes that AP cells early in life integrate genetic and metabolic cues through IGF2 to control their proliferation and resultant development of functional adipose, critical for long term metabolic resilience.

  单细胞
• VisiumHD of EVOV treated GSCs
  GSE308834Homo sapiens4 个样本2026-10-26

  Humanized mice were implanted with patient-derived glioblastoma stem-like cells (GSCs) tumor and treated with control (EV) or treatment (EVOV).

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