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。

• Single-cell Characterization of DNA Hydroxymethylation of the Mouse Brain [5hmC]
  GSE314195Mus musculus479 个样本2026-10-29

  DNA methylation, particularly CpG methylation, plays a pivotal role in brain development, function, and aging. While recent single-cell brain methylome atlases have been mapped, they cannot distinguish between 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) due to their reliance on bisulfite conversion. This limitation is particularly problematic in the brain, where postmitotic neurons accumulate abundant 5hmCG, which may exert functions opposite to 5mCG. Consequently, how CpG modifications regulate neuronal gene expression remains incompletely understood. To address this, we present Joint-Cabernet, a bisulfite-free single-cell platform enabling simultaneous profiling of 5hmC, 5mC, and transcriptomes. Applying Joint-Cabernet to nuclei from adult mouse brains, we resolved cell-type-specific DNA hydroxymethylation landscapes, revealing elevated 5hmCG and 5hmCH levels in transcriptionally active genes and regulatory elements across diverse brain cell types and spatial gradients in cortical layers. This single-cell multi-omic atlas (DNA methylation, hydroxymethylation, and transcriptome) of the mouse brain provides a framework for studying methylation-driven regulation in the brain organization and neurodegenerative diseases.

  单细胞空间转录组细胞图谱多组学
• Tau A152T risk variant drives distinct cell type transcriptional signatures in AD and PSP
  GSE350921Homo sapiens28 个样本2026-10-28

  The A152T point mutation is a rare genetic variant in the tau gene (MAPT) that is linked to risk of Alzheimer’s disease (AD) and frontotemporal dementia spectrum disorders, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). To uncover mechanisms through which the A152T variant contributes to risk of tauopathy, we performed single-nucleus RNA sequencing (snRNA-seq) on postmortem brain tissue collected from A152T carriers and pathology-matched non-carriers with either AD or PSP, along with age-matched controls. These efforts revealed that despite similar cell type composition across groups, A152T carriers exhibited distinct cell type-specific transcriptional changes in both AD and PSP. Differential expression analysis identified excitatory neurons, oligodendrocytes and astrocytes as the most affected cell populations in AD and PSP, and these same cell types showed the strongest A152T-specific changes. These findings identify transcriptional alterations that differentiate sporadic AD and sporadic PSP from AD-A152T and PSP-A152T, as well as shared molecular signatures unique to A152T carriers in both PSP and AD. Donor-level pseudobulk analyses showed broad directional support with the single-nucleus findings, although the proportion of donor-supported genes varied across cell type and comparison. Importantly, merging sporadic and A152T cases into a single disease group was found to mask transcriptional differences in several cell types in both AD and PSP, indicating divergence in transcriptional signature and highlighting the importance of screening for genetic risk variants like A152T in snRNA-seq data from human cohorts.

  单细胞
• A High-Throughput Functional 3D Droplet Microfluidic Platform for Function-to-Transcriptome Profiling Identifies Candidate lncRNAs Associated with Engineered NK Cell Function
  GSE343647Homo sapiens12 个样本2026-10-28

  Background: Natural killer (NK) cell–based immunotherapies show considerable promise for cancer treatment; however, their efficacy against solid tumors remains limited by functional heterogeneity and the restrictive tumor microenvironment. Engineered NK cells, including mesothelin-directed chimeric antigen receptor cytokine- induced memory-like (MSLN-CAR CIML) NK cells, exhibit enhanced cytotoxic potential, yet the transcriptional programs underlying effective tumor killing remain poorly defined. Although protein-coding regulators of NK cell function have been extensively studied, the contribution of long non-coding RNAs (lncRNAs) to cytotoxic NK cell states remains largely unexplored, particularly in engineered NK cell therapies. Methods: To address this gap, we developed and applied a three-dimensional (3D) Matrigel-based droplet microfluidic screening platform that enables single-cell resolution analysis of NK–tumor interactions. Unlike conventional bulk transcriptomic approaches, this function-to-transcriptome workflow enables functional isolation of killer and non-killer NK-cell populations prior to transcriptomic profiling enabling the direct comparison of transcriptional programs associated with cytotoxic function while minimizing confounding effects of bulk population analyses. Using this approach, we profiled donor-matched MSLN-CAR CIML NK cells and CIML NK controls from three independent donors. Results: Comparative transcriptomic analysis revealed widespread differences in lncRNA expression between killer and non-killer NK cell populations, characterized predominantly by broad lncRNA downregulation that was consistently observed across donors and more pronounced in MSLN-CAR CIML NK cells than in CIML controls. Integrated lncRNA-mRNA analyses prioritized candidate lncRNA–gene pairs based on genomic proximity and coordinated co-expression patterns, identifying several lncRNAs associated with cytotoxic gene programs. These transcriptional signatures were further associated with enrichment of cytotoxic and inflammatory pathways characteristic of highly functional NK cell states. Conclusions: Together, these findings demonstrate the utility of our functional droplet microfluidic screening platform in prioritizing candidate lncRNAs associated with cytotoxic NK cell states within matrix-restricted tumor environments. By integrating functional phenotyping with transcriptomic profiling, this platform provides a framework for identifying candidate lncRNA and other potential biomarkers associated with cytotoxic NK states for future mechanistic validation and the rational optimization of NK cell–based immunotherapies for solid tumors.

  单细胞
• Immune landscape and intercellular crosstalk in the cornea of an autoimmune-mediated dry eye disease
  GSE333335Mus musculus2 个样本2026-10-28

  We have employed a single cell sequencing approach using 10x genomis scRNAseq to study the immune composition in autoimmune induced dry eye cornea. This study found a diverse immune cell composition, including T cells, B cells, neutrophils and macrophages. Moreover, we characterized cell signaling communication networks between immune and epithelial and stormal cells.

  单细胞
• Tissue engineering polymeric formulations enable lymphangiogenesis for myocardial repair
  GSE330459Rattus norvegicus6 个样本2026-10-28

  We performed single-cell RNA sequencing (scRNA-seq) to profile the transcriptional landscape of ventricular tissue in a Sprague-Dawley rat model of myocardial ischemia/reperfusion (I/R). Two groups were analyzed: an I/R control group and a group treated with the pro-lymphangiogenic polymeric formulation PD-DN. Ventricular tissues were collected from both groups at three time points post-injury — 3, 5, and 7 days — to capture the temporal dynamics of cardiac repair. Single-cell suspensions were processed using the 10x Genomics Chromium platform with Illumina NovaSeq sequencing. Our analysis revealed temporally orchestrated changes in endothelial, immune, and fibroblast cell populations. The data provide insights into how PD-DN-driven lymphangiogenesis reprograms the cardiac microenvironment to facilitate functional recovery.

  单细胞
• Med1 Deletion Reprograms Dental Epithelium into Primitive Hair-Forming Epidermal Architecture via Trp63 Driven Epigenetic Alterations
  GSE316847Mus musculus1 个样本2026-10-28

  Ectodermal fate decisions between tooth enamel and skin hair are governed by transcription factors, epigenetic mechanisms, and tissue architecture. Deletion of the Mediator subunit Med1, which links enhancer activity to transcriptional output, induces a striking lineage conversion characterized by ectopic hair formation in mouse incisors. Here, we define the cellular, transcriptional, and epigenetic mechanisms underlying this process. Single-cell and spatial transcriptomic analyses reveal extensive remodeling of the incisor epithelium following Med1 deletion, whereby dental pre-ameloblasts and SI cells convert into hair germ–like populations resembling ancestral hair-initiating cells while retaining dental identity. Epidermal fate is driven by the master regulator Trp63, enabling hair formation without follicles distinguishing this process from canonical skin hair regeneration. Mechanistically, epigenetic changes occur in which TRP63 co-localized with alternative MED12-containing enhancers to activate itself and downstream epidermal genes. Together, these findings suggest that Med1 loss promotes hair formation through unique reprogramming to an evolutionarily primitive epidermal state rather than direct trans-differentiation to skin epithelium, providing new insights in ectodermal plasticity.

  单细胞空间转录组
• Med1 Deletion Reprograms Dental Epithelium into Primitive Hair-Forming Epidermal Architecture via Trp63 Driven Epigenetic Mechanisms
  GSE316208Mus musculus12 个样本2026-10-28

  Ectodermal fate decisions between tooth enamel and skin hair are governed by transcription factors, epigenetic mechanisms, and tissue architecture. Deletion of the Mediator subunit Med1, which links enhancer activity to transcriptional output, induces a striking lineage conversion characterized by ectopic hair formation in mouse incisors. Here, we define the cellular, transcriptional, and epigenetic mechanisms underlying this process. Single-cell and spatial transcriptomic analyses reveal extensive remodeling of the incisor epithelium following Med1 deletion, whereby dental pre-ameloblasts and SI cells convert into hair germ–like populations resembling ancestral hair-initiating cells while retaining dental identity. Epidermal fate is driven by the master regulator Trp63, enabling hair formation without follicles distinguishing this process from canonical skin hair regeneration. Mechanistically, epigenetic changes occur in which TRP63 co-localized with alternative MED12-containing enhancers to activate itself and downstream epidermal genes. Together, these findings suggest that Med1 loss promotes hair formation through unique reprogramming to an evolutionarily primitive epidermal state rather than direct trans-differentiation to skin epithelium, providing new insights in ectodermal plasticity.

  单细胞空间转录组
• Electroconductive Patch Promotes Heart Repair by Directing Epicardial Cell Fate towards Endothelial Lineage
  GSE311450Mus musculus10 个样本2026-10-28

  By developing patches whose electroconductivity matches native myocardium (cardiac electroconductivity-matched patches, CemPs), we show that WT1⁺ EPDCs convert into functional endothelial cells within 14 days of MI, and increase infarct vascular density in adult mice.We employed genetic fate-mapping approaches in WT1CreERT2 H11ZsGtd mice to trace the origin of the newly generated endothelial cells, and combined with single-cell transcriptomics further identifies a previously uncharacterized transitional state cells which is voltage-sensitive and commits to the endothelial lineage via TRPC3–Ca²⁺ signaling.This work elucidates the relationship between the electrical conductivity of biomaterials and the endothelial differentiation potential of WT1⁺ EPDCs, clearly defining the cellular origin of electroconductive patch-induced angiogenesis in adult mammals post-MI.

  单细胞
• Alternative splicing plays an important role in fast chemical reprogramming [scRNA-Seq]
  GSE292990Mus musculus2 个样本2026-10-28

  To investigate the role of Ptbp3 during reprogramming, scRNA-seq was carried out with RNAs isolated from the reprogramming intermediates transfected with shNC or shPtbp3.

  单细胞
• Spatial transcriptomic profiling of human left ventricular tissue in ischaemic heart disease and dilated cardiomyopathy
  GSE351778Homo sapiens2 个样本2026-10-27

  Spatially resolved single-cell gene expression profiling was performed on fresh-frozen human left ventricular tissue from one ischaemic heart disease (IHD) and one dilated cardiomyopathy (DCM) specimen. The Xenium Human Multi-Tissue and Cancer Gene Expression panel supplemented with 100 custom probes was used to characterise cardiomyocytes and cardiac fibroblasts and investigate spatial relationships between fibroblast subpopulations and cardiomyocyte.

  单细胞空间转录组
• Study of LETT@MVs‑induced ferroptosis in tumor cells via supplementation of PUFA
  GSE351467Homo sapiens4 个样本2026-10-27

  Ferroptosis represents a promising therapeutic strategy for cancer, yet its anti‑tumor efficacy is largely limited by insufficient polyunsaturated fatty acids (PUFA) within the tumor microenvironment (TME). Aloe vera thylakoid membranes, naturally rich in PUFA, are an ideal source to facilitate robust lipid peroxidation. To address biological delivery obstacles, we constructed tumor‑targeting biomimetic microvesicles (LETT@MVs) by engineering aloe‑thylakoid‑derived microvesicles (TDMVs) with the multifunctional peptide LETT, which enables tumor‑targeted delivery and lysosomal escape. We systematically characterized the influences of LETT@MVs on hepatocellular carcinoma (HCC) cells, including cell viability, vasculogenic mimicry (VM) formation, lipid peroxidation and ferroptosis in vitro. Antitumor potency and biosafety were further validated using an orthotopic HCC mouse model. Mechanistically, multi‑omics strategies combining bulk RNA‑seq, metabolomics and scRNA‑seq were applied to decipher underlying molecular events. LETT@MVs were effectively internalized by HCC cells and successfully escaped lysosomal degradation. Taking advantage of endogenous PUFA stored in thylakoid components, LETT@MVs triggered potent lipid peroxidation and ferroptosis, meanwhile remodelled the extracellular matrix (ECM) to suppress vasculogenic mimicry. In orthotopic HCC mice, LETT@MVs markedly retarded tumor growth via ferroptosis induction and VM repression without obvious safety risks. Integrated multi‑omics data demonstrated that LETT@MVs rewired transcriptional and metabolic profiles of HCC cells, driving highly‑metabolic tumor cells toward ferroptotic stress status and generating near‑death cell subpopulations. Collectively, our work validates that aloe‑thylakoid‑originated biomimetic nanoplatform can trigger robust tumor ferroptosis through PUFA supplementation, providing new clues to conquer ferroptosis resistance and advance therapeutic interventions for hyper‑metabolic tumors.

  单细胞
• Microglial lipid signaling drives glioblastoma invasion and represents a therapeutic vulnerability
  GSE348401Mus musculus8 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
• 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
• ScRNA-seq reveals cellular heterogeneity in urethral stricture
  GSE347480Homo sapiens6 个样本2026-10-27

  Urethral strictures are characterized by fibrotic scar tissue formation in the urethra, leading to difficulties in urination and potential renal dysfunction. The cellular microenvironment contributes to stenosis. However, the heterogeneity of key cell types hinders our understanding of this disease. Single-cell RNA sequencing was performed on three urethral scar tissues and three normal urethral tissues. First, the main cell types and sample heterogeneity were identified. Transcription factor (TF) and enrichment analyses were used to characterize the transcriptional regulation and metabolic patterns of fibroblasts and mast cells. Finally, CellChat was used to elucidate intercellular communication networks in urethral scar tissues. Of the eight cell types detected, fibroblasts, mast cells, and macrophages were major contributors to urethral scar tissue. These cells were categorized into seven (FB0–FB6), two (Mast0 and Mast1), and nine (Macro0-Macro8) subclusters, respectively, based on heterogeneity. Urethral scar tissue exhibited increased proportions of FB3 fibroblast, Mast1 mast cell, Macro1, and Macro7 counts. Marker genes of these subclusters facilitated the dysregulation of fibrosis through various biological processes, including cell adhesion and extracellular matrix organization. Additionally, screening of the dysregulation of multiple TFs and metabolic pathways revealed potential candidate TFs—ETS1 (from FB3) and SMAD3 (from Mast1)—associated with fibrosis. Furthermore, communication substantially increased between fibroblasts and other cells, and between Macro1 or Macro7 and other macrophage subclusters or fibroblasts in urethral scar tissue. We revealed the transcriptional characteristics of key cells involved in the fibrogenesis of urethral stricture, which elucidates the pathogenesis of urethral stenosis and advances the exploration of therapeutic targets.

  单细胞
• Molecular Imaging of the TGF-β Activating Integrin avb6 Detects Chronic Lung Allograft Dysfunction
  GSE346597Mus musculus2 个样本2026-10-27

  TGF-β-activating integrins promote solid-organ fibrosis, suggesting their potential as disease markers. Chronic lung allograft dysfunction (CLAD), a progressive fibrotic complication that limits lung transplant survival, is driven by intragraft TGF-β activation. However, TGF-β-activating integrin expression patterns remain undefined in lung transplants. Single-cell RNA sequencing and proteomic analysis of tissue specimens from a mouse CLAD model and human explanted lungs with CLAD revealed high levels of the TGF-β-activating integrin αvβ6, primarily localized to fibrosis-associated Keratin 8+ alveolar transitional epithelial cells, which were greatly reduced in tolerant lungs. Molecular imaging with a newly optimized positron emission tomography radiotracer specific for avb6, [64Cu]Cu-DOTA-A20-K16R, showed significantly higher uptake in CLAD than in tolerant transplants. [64Cu]Cu-DOTA-A20-K16R activity was also reduced by experimental treatments that lowered avb6 expression and inhibited CLAD severity. Finally, [64Cu]Cu-DOTA-A20-K16R autoradiographic analysis of human explanted lungs with CLAD showed elevated activity that correlated with increased avb6 expression. Collectively, these findings illustrate the potential utility of αvβ6 molecular imaging for detecting CLAD pathogenesis.

  单细胞
• 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
• Single-cell profiling of microglia transcriptomes transduced by the AAV-MSRE tool
  GSE345675Mus musculus9 个样本2026-10-27

  This study profiles the transcriptomic responses of microglia transduced with the AAV-MSRE tool at single-cell resolution. Single-cell RNA sequencing was used to characterize transduced microglial populations, assess their molecular identities, and evaluate transcriptional changes associated with AAV-MSRE delivery. These data provide a resource for examining the cellular specificity and transcriptomic impact of AAV-MSRE-mediated targeting in microglia.

  单细胞
• Transcriptomic profiling of M1-like and M2-like mouse bone marrow-derived macrophages
  GSE344431Mus musculus6 个样本2026-10-27

  Macrophage activation states are involved in intestinal inflammation and tissue remodeling, but the transcriptional programs linking macrophage polarization to ulcerative colitis-associated molecular changes remain incompletely characterized. In this study, primary bone marrow-derived macrophages from mice were polarized toward M1-like or M2-like states and subjected to bulk RNA sequencing. M1-like polarization was induced using lipopolysaccharide and interferon-gamma, whereas M2-like polarization was induced using interleukin-4 and interleukin-13. Three biological replicates were analyzed per group. The resulting transcriptomes were used to identify macrophage polarization-related genes and were subsequently integrated with ulcerative colitis macrophage single-cell transcriptomic and circulating proteomic evidence to prioritize disease-associated macrophage candidates.

  单细胞
• 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
• A single cell atlas defines perinatal factors that drive murine bone marrow development
  GSE318094Mus musculus2 个样本2026-10-27

  Processes that direct initial colonization and maturation of the bone marrow remain elusive, despite their importance to lifelong hematopoiesis. Bone marrow mesenchymal and stromal cell (BMSC) maturation must establish supportive hematopoietic niches prior to the recruitment and colonization of hematopoietic stem cells (HSCs). Here, we define the identity of murine BMSC progenitors and temporal nature of marrow colonization through a single cell atlas spanning late gestation through 18 months of age. We define progenitor cells and developmental trajectories for Cxcl12-abundant reticular (CAR) cells and osteoblasts within the marrow, including the emergence of direct and secreted signaling modalities that impact HSC quiescence and regenerative capacity. We further identify temporal changes in Early B Cell Factor (Ebf) 1-3 transcription factor expression and activity that correlate with niche establishment. These transcriptional activities relate to change to changes in systemic physiology, including metabolic, inflammatory, and hypoxic signaling, that direct CAR cell emergence after birth in mice. These findings provide unprecedented resolution to the colonization and maturation of the murine bone marrow environment.

  单细胞细胞图谱
• CEBPA-Induced Trophectoderm-like Cells from Pluripotent Stem Cells Enable Modeling of Trophoblast Lineage Specification [scRNA-Seq]
  GSE315752Mus musculus1 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.

  单细胞
• 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
• 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
• 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
• 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
• 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
• TNFR2 agonism increases tissue and effector Treg cells
  GSE344965Mus musculus12 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
• Recordanelles for transcriptome-wide single-cell RNA recording in human cells [dataset_2 RNA-Seq]
  GSE344934Homo sapiens48 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