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。

• Synapse-seq reveals cytotoxic CD4+ T cell suppression of human antibody responses
  GSE351507Homo sapiens22 个样本2026-10-27

  Deciphering the molecular dialogue between cells is central to understanding how immune responses are orchestrated. Here we applied Synapse‐seq, a new image‐enabled cell interaction sorting and transcriptomic profiling approach, to characterize CD4+ T-B cell synaptic interactions in human spleen organoids. We identified B cells synapsing with FOXP3+ regulatory T cells (Tregs) expressing high levels of perforin and granzymes A and B, indicating that cytotoxicity is a major mechanism of CD4+ Treg suppression of specific B cells. Antigen-specific Synapse-seq revealed opposing phenotypes of viral and autoreactive T-B interactions and identified a hemagglutinin-specific TCR-BCR pair in a human immune system. Both CD3+ and CD4+ T cell-specific knockouts of cytotoxic genes robustly increased antibody responses against both nuclear autoantigens and viral antigens. Consistent with these findings, patients with systemic lupus erythematosus (SLE) exhibited a significant enrichment of cytotoxic CD4+ Tregs. Our findings support cytotoxicity as a dominant way CD4+ T cells regulate B cells and antibody responses. More broadly, we suggest Synapse-seq as a generalizable method to characterize cell interactions without requiring cell engineering.
• TSC2-Mutant Yucatan Minipig Cardiac Rhabdomyoma Model Reveals mTORC1 Activation and MITF/TFE Expression Signature
  GSE349392Sus scrofa; Homo sapiens18 个样本2026-10-27

  Tuberous sclerosis complex (TSC) is an inherited tumor predisposition syndrome caused by pathogenic variants in TSC1 or TSC2. We generated a heterozygous TSC2-mutant Yucatan minipig carrying the recurrent pathogenic TSC2 p.Arg505* variant and characterized its cardiac phenotype using histopathology, immunohistochemistry, and RNA sequencing. TSC2-mutant minipigs developed multiple cardiac rhabdomyomas resembling human lesions. Comparative transcriptomic analyses identified a conserved TSC-associated expression program and MITF/TFE-regulated lysosomal pathways in human and minipig tumors.
• Genome-wide CRISPRi-seq profiling of essential-gene contributions to aminoglycoside susceptibility in Pseudomonas aeruginosa PAO1
  GSE349013Pseudomonas aeruginosa40 个样本2026-10-27

  This CRISPRi-seq dataset quantifies the abundance of 83,078 sgRNAs in a pooled Pseudomonas aeruginosa PAO1 CRISPRi library across untreated, aminoglycoside-treated and serum-containing conditions. Four independent experimental batches were used to measure untreated fitness, responses to tobramycin or amikacin, and fitness in 60% fetal bovine serum. The deposited processed data include raw guide counts and complete guide- and gene-level results for the predefined comparisons used in the study.

  扰动筛选
• RNA-seq analysis of CRISPRi-mediated gene silencing and tobramycin response in Pseudomonas aeruginosa PAO1
  GSE349001Pseudomonas aeruginosa18 个样本2026-10-27

  This RNA-seq dataset profiles transcriptional responses associated with CRISPRi-mediated partial silencing of atpI, accC, secA and ftsZ in Pseudomonas aeruginosa PAO1. A non-targeting CRISPRi control was profiled in parallel, including an additional condition exposed to 0.4 µg/mL tobramycin. Three independent biological replicates were analyzed per condition.
• Macrophage lipid signaling drives glioblastoma invasion and represents a therapeutic vulnerability
  GSE348147Mus musculus16 个样本2026-10-27

  Glioblastoma (GBM) is characterized by diffuse infiltration into the surrounding brain, limiting complete surgical resection, the strongest determinant of patient survival. The mechanisms driving this invasive growth remain incompletely understood. Here, we identify a lipid-mediated paracrine signaling axis through which tumor-associated microglia/macrophages promote glioma invasion. Integrating single-cell transcriptomics, spatial lipidomics, and functional perturbation across mouse models and human GBM samples, we show that invading tumor cells engage and reprogram myeloid cells via CSF1R–PI3K signaling. This induces lipid metabolic reprogramming and secretion of bioactive lipids, including lysophosphatidylcholines (LPCs) and lysophosphatidic acids (LPAs), which promote GBM invasion through distinct downstream pathways. Disruption of this myeloid–GBM axis, reduces lipid secretion and suppresses invasion. Targeting downstream LPA–LPAR or YAP/TAZ signaling further constrains invasion in a context-dependent manner. Together, these findings define a lipid-driven circuit linking the tumor microenvironment to glioma invasion and identify strategies to reduce infiltration and improve surgical resection.

  单细胞空间转录组扰动筛选
• A single-cell RNA sequencing atlas of postnatal ovarian development in dairy goats
  GSE345824Capra hircus10 个样本2026-10-27

  Postnatal ovarian development is a critical process that establishes ovarian reserve and determines female reproductive capacity. However, the cellular and molecular dynamics underlying early folliculogenesis in livestock species remain poorly characterized. Here, we generated a single-cell RNA sequencing dataset of dairy goat ovaries collected at postnatal days 4, 20, and 60, representing distinct stages of follicular development. This dataset comprises 90,770 high-quality single cells and 20,412 gene features, including six major ovarian cell populations with distinct transcriptional signatures. The dataset provides comprehensive transcriptomic profiles of oocytes, granulosa cells, theca cells, stromal cells, endothelial cells, and immune cells during early ovarian development. Cell-level annotations, sample information, and gene expression count matrices are provided to facilitate investigation of ovarian cellular heterogeneity, folliculogenesis, and cell-cell communication.

  单细胞细胞图谱
• RNA-seq data from hypothalamic tissues of male and female Japanese quail embryos.
  GSE338413Coturnix japonica12 个样本2026-10-27

  Total RNA was extracted from E12 hypothalamic tissues of male, female, vehicle-treated male, and EB-treated male embryos. Transcriptomes were analyzed by RNA sequencing.
• Regulatory T Cell Instability Facilitates Blood-Brain Barrier Disruption via the β-catenin-Tight Junctions Axis, Leading to Perioperative Neurocognitive Disorders
  GSE337348Homo sapiens12 个样本2026-10-27

  Perioperative neurocognitive disorders (PND) are significant neurological complications in elderly surgical patients, yet the underlying immune-mediated mechanisms remain elusive. Blood-brain barrier (BBB) disruption is increasingly recognized as a critical neurovascular event in PND and may result from perioperative immune dysregulation. Regulatory T cells (Tregs) are key mediators of neurovascular homeostasis and BBB integrity. We therefore investigated whether perioperative Treg instability contributed to BBB disruption and PND. Single-cell transcriptomic profiling of perioperative PBMCs from elderly surgical patients revealed marked remodeling of the CD4+ T cell compartment, characterized by disproportionate Treg loss and functional destabilization. Tregs shifted from resting and immunosuppressive states toward an inflammatory phenotype, accompanied by reduced expression of regulatory and tissue-reparative genes, including FOXP3, CTLA4, PDCD1, and AREG. Comparative transcriptomic analysis of Tregs identified 34 dexmedetomidine-corrected genes, with CTNNB1, encoding β-catenin, emerging as the dominant hub within the protein-protein interaction network. These findings implicated impaired β-catenin signaling as a central driver of perioperative Treg destabilization. Mouse hippocampal scRNA-seq revealed postoperative endothelial remodeling characterized by reduced S1pr1 and Cldn5 and increased Icam1 expression. In a murine PND model, β-catenin activation restored postoperative Treg abundance and regulatory gene expression while preserving hippocampal endothelial barrier programs, as evidenced by increased S1PR1 and Claudin-5 and reduced ICAM1 expression. These protective effects were abolished by PC61-mediated Treg depletion, indicating a Treg-dependent mechanism. Furthermore, restoration of Treg homeostasis with recombinant PD-L1 preserved ultrastructural BBB integrity, reduced Evans blue-defined BBB leakage, attenuated hippocampal neuroinflammation, and improved cognitive function. These findings identify perioperative Treg instability as a key immune driver of BBB disruption and cognitive dysfunction in PND, and establish Treg β-catenin signaling as a potential therapeutic target for preserving neurovascular integrity.

  单细胞
• Bulk RNA-seq of monocytes from systemic lupus erythematosus samples
  GSE326771Homo sapiens10 个样本2026-10-27

  This study profiled bulk RNA-seq from human monocyte samples derived from individuals with systemic lupus erythematosus. Total RNA was extracted and sequenced to characterize transcriptomic features in SLE monocytes. Raw gene-level count matrices, gene annotation, and sample-level metadata are provided.
• Bulk RNA-seq of IFN-treated and untreated healthy control neutrophils
  GSE326770Homo sapiens12 个样本2026-10-27

  This study profiled bulk RNA-seq from human neutrophils derived from healthy control donors under untreated and IFN-treated conditions. Total RNA was extracted and sequenced to characterize transcriptional responses associated with IFN exposure. Raw and normalized gene-level count matrices, along with sample-level metadata and gene annotation files, are provided.
• C-Met controls CD8+ T cell-mediated anti-tumor immunity
  GSE319458Mus musculus12 个样本2026-10-27

  The hepatocyte growth factor (HGF)/c-Met axis is a major oncogenic pathway, yet how it shapes cytotoxic T cell function remains unclear. Here, we show that c-Met identifies a transcriptionally and functionally distinct subset of tumor-reactive CD8⁺ T cells, while HGF suppresses their effector function. Using Pmel-1 CD8⁺ T cells and a CD8⁺ T cell–specific c-Met knockout, RNA sequencing revealed c-Met⁺ CTLs are enriched for cytotoxic, interferon, TCR signaling, and inflammatory programs, whereas HGF induces immunoregulatory pathways, including IL-13–STAT3/STAT6, and downregulates effector genes. Functionally, c-Met⁺ CTLs displayed enhanced antigen-specific killing and superior tumor control, with increased degranulation and lower inhibitory checkpoint expression. HGF or c-Met deficiency restrained these responses. These findings identify c-Met as a marker of highly cytotoxic CD8⁺ T cells and reveal HGF as a key suppressor of CTL function in cancer providing a mechanistic framework for HGF-driven immune suppression in cancer.
• CEBPA-Induced Trophectoderm-like Cells from Pluripotent Stem Cells Enable Modeling of Trophoblast Lineage Specification
  GSE315751Mus musculus28 个样本2026-10-27

  Trophoblast lineages are essential for placental development and play indispensable roles in mammalian development. However, the regulatory mechanisms governing trophoblast lineage specification, particularly trophectoderm formation, remain elusive. Here, we show that transient overexpression of the transcription factor Cebpa in mouse pluripotent stem cells efficiently generates trophectoderm-like cells that recapitulate key transcriptional features of trophectoderm. These trophectoderm-like cells can be further induced to form trophoblast organoids and exhibit developmental competence to generate all trophoblast lineages in vitro. Mechanistically, Cebpa overexpression drives extensive epigenetic reprogramming toward a trophectoderm-like state, including global remodeling of chromatin accessibility and coordinated changes in H3K4me3 and H3K27me3 histone modifications. CUT&RUN analyses further reveal binding of CEBPA to multiple trophectoderm-specific enhancers. Together, our findings identify Cebpa as a potent inducer of trophectoderm potential and establish a new platform for modeling trophectoderm lineage specification in vitro.
• CEBPA-Induced Trophectoderm-like Cells from Pluripotent Stem Cells Enable Modeling of Trophoblast Lineage Specification [RNA-Seq]
  GSE315750Mus musculus14 个样本2026-10-27

  Trophoblast lineages are essential for placental development and play indispensable roles in mammalian development. However, the regulatory mechanisms governing trophoblast lineage specification, particularly trophectoderm formation, remain elusive. Here, we show that transient overexpression of the transcription factor Cebpa in mouse pluripotent stem cells efficiently generates trophectoderm-like cells that recapitulate key transcriptional features of trophectoderm. These trophectoderm-like cells can be further induced to form trophoblast organoids and exhibit developmental competence to generate all trophoblast lineages in vitro. Mechanistically, Cebpa overexpression drives extensive epigenetic reprogramming toward a trophectoderm-like state, including global remodeling of chromatin accessibility and coordinated changes in H3K4me3 and H3K27me3 histone modifications. CUT&RUN analyses further reveal binding of CEBPA to multiple trophectoderm-specific enhancers. Together, our findings identify Cebpa as a potent inducer of trophectoderm potential and establish a new platform for modeling trophectoderm lineage specification in vitro.
• 3D genome remodeling directs in vitro human hematopoietic development and predicts disease trait genetics
  GSE311714Homo sapiens14 个样本2026-10-27

  The 3D genomic architecture provides a regulatory scaffold for cell fate transitions, yet how chromatin architecture directs human hematopoietic development remains poorly understood. The endothelial-to-hematopoietic transition (EHT) is the developmental gateway by which specialized hemogenic endothelial cells generate definitive hematopoietic stem and progenitor cells (HSPCs), which go on to support blood cell production throughout mammalian life. Understanding mechanisms that regulate EHT is critical for blood disease modeling and regenerative medicine applications. Using a human induced pluripotent stem-cell (iPSC) hematopoiesis model, we combined single-nucleus RNA-seq, ATAC-seq, and Hi-C to chart chromatin reorganization during hemogenic specification and EHT. Hierarchical reorganization of topologically associating domains (TADs) and sub-TAD structures accompany the morphological conversion of endothelial sheets into HSPCs. Dynamic TAD and sub-TAD reorganization precedes transcriptional activation of key hematopoietic regulators (e.g., RUNX1, CEBPA), revealing a structural logic by which genome topology anticipates formation of cis-regulatory elements and transcription factor programs that control hematopoietic development. For example, we identify modulation of dynein and kinesin molecular motor genes during EHT. Functional dynein inhibition promotes EHT, likely through unopposed activities of kinesin motors. Integration of single cell data with Hi-C and genome-wide association study (GWAS) loci reveals enrichment for blood and immune trait variants, connecting 3D genome remodeling during in vitro hematopoiesis to in vivo human disease genetics. Together, these findings define the regulatory architecture of blood cell emergence and establish iPSC differentiation as a tractable platform for interrogating 3D genome principles in human development and disease. More broadly, our integrated data across rare developmental cell types helps define 3D chromatin regulatory architecture that underlies human GWAS variation.

  单细胞
• p53 preserves chromosome stability in dividing cells under hypo-osmotic stress
  GSE311220Homo sapiens30 个样本2026-10-27

  Cells respond to frequent osmotic stress to maintain structural integrity and function. Whereas acute volume regulation is well-known, the cellular response to prolonged osmotic stress and its long-term consequences remain poorly understood. In this study, we investigate how lasting hypo-osmotic stress influences cell proliferation and the associated cellular response. We observe that cells undergoing their first division under hypo-osmotic stress experience delayed mitotic entry, lengthened mitotic duration, elevated mitotic errors and aneuploidy formation. However, continued cell division is halted through a p53/p21-dependent G1 arrest. p53 activation occurs post-mitotically and is associated with loss of perichromosomal layer (PCL), defective chromosome decondensation and impaired nuclear expansion in daughter cells after mitotic exit. We show that the altered nuclear size dynamics lead to nuclear accumulation of p53 and activation of downstream gene expression. These findings uncover a mechanosensitive, p53-mediated mechanism that safeguards chromosome integrity by suppressing erroneous mitosis under hypo-osmotic stress.
• Endogenous variability in transcription factor concentrations shapes their genome-wide occupancy [ChIP-seq]
  GSE308325Mus musculus44 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.
• Chemically Defined Differentiation of Human PSCs to Definitive Hematopoietic Progenitors
  GSE304432Homo sapiens21 个样本2026-10-27

  This study investigates hematopoietic differentiation of human pluripotent stem cells (hPSCs) using a chemically defined differentiation system. RNA-seq was used to characterize cell populations generated during differentiation, including adherent supportive cells and suspension hematopoietic populations. The newly submitted samples provide additional transcriptomic profiling of FACS-sorted CD34+CD38-CD45RA-CD90+CD49f+ cells isolated from the suspension hematopoietic population and complement the other samples .
• SAA-expressing hepatocytes as a key liver cell population in Alcohol associated Hepatitis
  GSE304325Homo sapiens13 个样本2026-10-27

  This study describes the dynamics of cellular heterogeneity during the progression of ALD to AH at a single cell level. Moreover, we have identified the specific subpopulations enriched in AH. This condition is characterized by an expansion of proinflammatory SAA+ hepatocytes, which strongly interact with hyperactivated neutrophils, suggesting a potential mechanism that could contribute to the exacerbated inflammation that characterizes this disease.

  单细胞
• Effect of senescent cells on macrophage polarisation
  GSE296922Homo sapiens10 个样本2026-10-27

  Senescent cells (SCs) accumulate with age and injury and express a pro-inflammatory/pro-fibrotic secretome, termed the senescence-associated secretory phenotype (SASP). Hence, accumulation of senscent cells can lead to inflammation and organ fibrosis. To investigate effects of SASP factors on macrophage polarisation macrophages matured from healthy donor blood monocytes were exposed to control or senescent cell conditioning media for 24 hours. Senescent cell media was derived from human proximal tubular epithelial cells (PTECs) exposed to 10 Gy of ionising radiation to induce senescence in vitro.
• sn-multiome of psoriasis skin
  GSE294957Homo sapiens18 个样本2026-10-27

  We simultaneously profile the gene expression and chromatin accessibility of lesional skin of psoriasis to understand the epigenetic landscape that regulates gene expression in the psoriatic skin

  多组学
• Single Cell multi-omics identifies VEGFA-mediated angiogenesis results in relapse in Sonic Hedgehog Medulloblastoma [snRNA-seq]
  GSE287109Homo sapiens12 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
• Single Cell multi-omics identifies VEGFA-mediated angiogenesis results in relapse in Sonic Hedgehog Medulloblastoma
  GSE287108Homo sapiens13 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
• Expression profile of tumor suppressive miR-34a- and DNA demethylase TET1-overexpressing MDA-MB-231 metastatic breast cancer cell lines in response to MCTS1 enrichment
  GSE247305Homo sapiens12 个样本2026-10-27

  Small, single-stranded, non-coding microRNA-34a (miR-34a) has been reported to inhibit tumorigenesis in many types of cancers. We previously reported that miR-34a is one of the most upregulated miRNAs upon the depletion of Malignant T-cell amplified sequence (MCT-1 or MCTS1), a proto-oncoprotein containing RNA-binding domain PUA. We hypothesized that MCTS1 inhibits miR-34a expression by downregulating DNA demethylation machinery, ten eleven translocation 1 (TET1). By using RNA-seq, we aimed to dissect differential downstream targets implicated by abberant MCTS1 in breast cancer cells with enrichment of tumor suppressors miR-34a and TET1.
• Cytoprotective Effects of Quercetin on Antibiotics- and Antimycotics-Induced Toxicity in Human Corneal Epithelial Cells: Cellular Responses and Transcriptomic Mechanisms
  GSE351741Homo sapiens12 个样本2026-10-26

  Quercetin, a plant-derived dietary flavonoid with well-studied antioxidant properties, was shown to have cytoprotective effects against several cytotoxic drugs, yet its potential for antimicrobial-induced cytotoxicity on corneal epithelium remains unexplored. The corneal epithelium, in synergy with the secretions of lacrimal and meibomian glands, maintains the ocular surface homeostasis and integrity. Constant environmental exposure predisposes the ocular surface to microbial keratitis, which is routinely treated with antibiotics and antimycotics. Prolonged use of antimicrobials induces epithelial cell death and chronic conditions such as dry eye disease. In this study, human corneal epithelial (HCE) cells were treated with the antibiotics ciprofloxacin (CIP) and moxifloxacin (MXF) and the antimycotics fluconazole (FLU) and natamycin (NAT), alone and in combination with quercetin, and cytotoxicity, apoptotic markers, and whole-transcriptome changes were assessed. All four antimicrobials induced significant, concentration-dependent cytotoxicity at therapeutic doses, evidenced by apoptotic morphology, elevated BAX/Bcl-2 ratio, and increased sub-G0/G1 and Annexin V-positive populations. Quercetin co-treatment markedly attenuated cell death by reversing apoptotic signatures and transcriptomic reversal of multiple antimicrobial-induced signaling pathways. These findings demonstrate the cytoprotective capacity of the natural antioxidant quercetin against antibiotic- and antimycotic-induced cytotoxicity in HCE cells, supporting its translational potential as a natural antioxidant adjuvant in antimicrobial ophthalmic formulations.
• Transcriptomic profiling of Niemann-Pick disease type C (NPC1-mutant) patient fibroblasts and healthy control fibroblasts with and without Fingolimod treatment
  GSE351603Homo sapiens12 个样本2026-10-26

  Niemann-Pick disease type C (NPC) is a rare lysosomal storage disorder caused by mutations in NPC1, which impair cholesterol export from late endosomes/lysosomes and lead to progressive neurodegeneration. How lysosomal cholesterol trafficking failure translates into broader cellular dysfunction, and whether it can be pharmacologically reversed, remains poorly understood. Fingolimod (FTY720), an FDA-approved sphingosine-1-phosphate receptor modulator, has been reported to improve lipid trafficking in NPC1-deficient cells. To define the transcriptional consequences of NPC1 deficiency and the response to Fingolimod, we performed bulk RNA-seq on primary skin fibroblasts from an NPC patient and a healthy control, each untreated or treated with Fingolimod. NPC fibroblasts showed widespread transcriptional reprogramming compared with healthy control fibroblasts, including dysregulation of lysosomal, autophagy and cholesterol homeostasis genes, activation of innate immune and interferon-stimulated genes, altered DNA repair gene expression, loss of fibroblast identity programs, and induction of a transcriptomic aging signature. Fingolimod treatment partially reversed many of these disease-associated changes in NPC fibroblasts, shifting the transcriptome toward that of healthy controls and reducing the transcriptomic aging score, and also lowered the aging score in healthy control fibroblasts. These data support a link between lysosomal cholesterol trafficking failure, innate immune activation and cellular aging signatures, and identify Fingolimod as a modulator of these programs.
• A GABA-producing Limosilactobacillus fermentum ameliorates autism-like behaviors associated with altered gut microbial metabolism and cortical GABA signaling
  GSE351532Mus musculus24 个样本2026-10-26

  Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social deficits and restricted, repetitive behaviors. Altered excitation/inhibition (E/I) balance, including impaired γ-aminobutyric acid (GABA) ergic signaling, has been implicated as a key pathophysiological feature of ASD. Although growing evidence implicates the gut–brain axis in regulating neural function, the strain-specific microbial mechanisms that influence central GABAergic signaling remain incompletely understood. Here, we evaluated whether Limosilactobacillus fermentum IMB064, identified by genome-based in silico screening, could modulate ASD-associated symptoms in BTBR mice, a widely used ASD model. Oral administration of IMB064 significantly reduced repetitive behaviors and improved social novelty preference in BTBR mice. Taxa-resolved metabolic flux modeling of the gut microbiome based on metagenomic profiling indicated that IMB064 administration was associated with alterations in gut microbial metabolic potential, including increased potential for GABA production, particularly among GABA-producing taxa such as Limosilactobacillus. Transcriptomic analysis further revealed a cortex-selective response to IMB064, with 1,552 cortical genes significantly altered and enriched in neuronal signaling pathways. These differentially expressed genes significantly overlapped with human ASD-associated cortical co-expression modules identified by weighted gene co-expression network analysis (WGCNA) and with chromatin-regulatory gene networks. Consistent with this region-specific molecular response, IMB064 significantly increased cortical GABA levels, with a trend toward an increased GABA-to-glutamate ratio, whereas no significant changes were observed in the striatum. Collectively, these findings indicate that the GABA-producing strain IMB064 alters gut microbial metabolic potential and is associated with cortex-selective changes in GABA-related neurochemical profiles, accompanied by modulation of human ASD-relevant gene networks and improvement of ASD-like behavioral phenotypes, supporting IMB064 as a promising live biotherapeutic candidate for ASD.

  计算与 AI
• TGF-β inhibition ameliorates reactive ALS astrocyte sub-states at single-cell resolution
  GSE351508Homo sapiens16 个样本2026-10-26

  In amyotrophic lateral sclerosis (ALS), astrocytes become reactive, ultimately contributing to neuron death. Upregulation of TGF-β signalling has been implicated in astrocyte-mediated neurodegeneration in ALS. However, whether TGF-β drives cell-autonomous astrocyte reactive transformation, potentially by altering astrocyte reactive substates, remains unknown. To address this, we inhibited TGF-β in hiPSC derived ALS astrocytes carrying VCP mutations, known to cause familial ALS, and performed single-cell RNA sequencing, single-cell proteomics and functional studies informed by our analysis. We identified changes in the proportion of transcriptomic reactive substates characterised by mitochondrial dysfunction and markers of reactive transformation. Importantly these substates selectively upregulated an isoform-restricted TGF-β2–betaglycan axis and were ameliorated following TGF-β inhibition. Single-cell mass spectrometry-based proteomics validated these findings, revealing a VCP mutant subpopulation featuring increased translation and proinflammatory protein expression, which was similarly abrogated by TGF-β inhibition. Finally, secretome profiling revealed an upregulation of inflammatory mediators in VCP mutant astrocyte conditioned media, and increased motor neuron apoptosis was rescued when TGF-β was inhibited in VCP mutant astrocytes. Together, our analysis reveals that human VCP mutant astrocytes feature dysregulated cell-autonomous reactive sub-states, driven by TGF-β activation, which partially recapitulate astrocyte dysregulation identified in patient postmortem single-cell studies. Inhibiting TGF-β rescues dysregulated VCP mutant sub-states and astrocyte-mediated neurotoxicity. These results collectively indicate that selective TGF-β pathway inhibition in astrocytes may be a potential therapeutic approach for ALS.

  单细胞
• Transmural Single-Nucleus Transcriptomics Nominates Candidate Disease Programs in Human Necrotizing Enterocolitis
  GSE351352Homo sapiens10 个样本2026-10-26

  Necrotizing enterocolitis (NEC) is a life-threatening disease of premature infants marked by inflammation, ischemia, mucosal injury, and, in advanced cases, necrosis extending into deeper layers of the intestinal wall. Because NEC affects specialized, interacting cells in a developing intestine, we used single-nucleus transcriptomics to build a transmural, cell-type-resolved map and nominate hypothesis-generating disease programs distinct from maturation. Full-thickness intestinal specimens from fetal/prenatal controls, acute NEC cases, and infant controls were analyzed by single-nucleus RNA sequencing (snRNA-seq). Fetal and infant samples served as developmental references. Analyses included cell annotation, NEC-versus-infant differential expression, gene ontology (GO), cross-lineage recurrence, cell-death signatures, and developmental maturity. We profiled 53,735 nuclei by snRNA-seq and resolved 34 epithelial, stromal, vascular, immune, neuronal, glial, and smooth-muscle populations. We used a morphology-based nuclei scoring system for sample selection that predicted high-quality transcript recovery. NEC nuclei were represented across this cellular landscape, with recurrent gene-expression changes suggesting shared inflammatory recruitment, antimicrobial/redox defense, stress adaptation, complement/vascular activation, reduced homeostatic signaling, and cell-death-associated regulation. Developmental maturity analysis identified fetal-like expression levels in subsets of NEC-regulated genes. Proliferative crypt populations retained DNA-repair/cell-cycle programs with inflammatory, hypoxic, and ER-stress features, while absorptive enterocytes showed reduced digestive, transport, detoxification, and terminal villus-function programs. Secretory-lineage changes implicated goblet mucus-barrier responses with reduced glycosylation, trafficking, and hydration; enteroendocrine changes in epithelial defense, metabolic stress, and neural signaling; and Paneth cell retention of antimicrobial effector transcripts despite altered ER quality control, autophagy, and granule delivery in NEC. Non-epithelial programs implicated stromal Wnt/BMP niche loss, impaired lymphatic drainage/scavenging, macrophage cytokine activation with reduced clearance machinery, neuroglial circuit defects, and altered smooth-muscle contraction-relaxation balance. This single nuclear intestinal cell atlas nominates multicellular programs that may govern NEC initiation, progression toward tissue destruction, and resolution toward functional recovery.

  单细胞细胞图谱
• RNA Polymerase II Dynamics in Antiviral NK Cell Responses [CUT&Run]
  GSE351044Mus musculus18 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.
• Gene therapies alleviate absence epilepsy associated with Scn2a deficiency in DBA/2J mice
  GSE349370Mus musculus10 个样本2026-10-26

  Loss-of-function (LoF) mutations in SCN2A, encoding the voltage-gated sodium channel NaV1.2, cause severe, often drug-resistant epilepsy. We generated Scn2agt/gt mice on the seizure-susceptible DBA/2J (D2J) background and identified prominent spontaneous absence seizures with short and long spike-wave discharges (SWDs), contrasting with the milder phenotype observed on the seizure-resistant C57BL/6N background. Restoring NaV1.2 expression in adult mice markedly reduced SWDs, supporting the potential of adult SCN2A gene replacement. RNA sequencing revealed broad downregulation of voltage-gated potassium channel genes, including Kcnal (KV1.1), which was also reduced in human cerebral organoids with SCN2A deficiency. AAV-mediated expression of human KV1.1 substantially reduced absence seizures in Scn2agt/gt mice. These findings demonstrate the influence of genetic background on SCN2A-associated epilepsy and identify NaV1.2 replacement and KV1.1 augmentation as potential therapeutic strategies.