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 RNA sequencing of appendiceal adenocarcinoma reveals a low proportion of epithelial cells and a fibroblast enriched tumor microenvironment
  GSE352702Homo sapiens4 个样本2026-10-31

  Appendiceal adenocarcinoma (AA) is an understudied gastrointestinal malignancy. Treatment is guided by its proximal counterpart, colorectal cancer (CRC), despite recent studies demonstrating AA’s unique mutational landscape and poor response to CRC chemotherapy. As the first application of single-cell technology to AA these data provide insight into the intratumor heterogeneity of AA and highlight the important contribution of the tumor microenvironment in this orphan disease. These results also reinforce multiple observations that AA is a unique disease entity from CRC and targeting the tumor microenvironment should be considered as a therapeutic strategy.

  单细胞
• Local and circulating cytotoxic CD4 T cells are early markers of disease activity in pediatric Crohn’s disease
  GSE352630Homo sapiens8 个样本2026-10-31

  Inflammatory bowel disease (IBD) requires improved molecular and cellular stratification to guide therapy. In the PREDICT study, we profiled intestinal and blood T cells from treatment-naïve pediatric patients with IBD, disorders of gut–brain interaction controls, and healthy donors using single-cell RNA sequencing. Across 107 participants, we identify a population of clonally expanded cytotoxic CD4 T cells (CD4 CTL) enriched in the inflamed gut of patients with Crohn's disease (CD) and ulcerative colitis. Cell–cell interaction analyses and validation in a mouse model implicate IL-27 in CD4 CTL differentiation. Elevated CD4 CTL frequencies in gut and peripheral blood at diagnosis are associated with subsequent poor outcome of anti-TNF therapy in pediatric CD. Findings in our identification cohort are validated in an independent cohort and through reanalysis of published datasets. Blood CD4⁺CXCR6⁺CD27⁻ T cells displayed a CD4 CTL transcriptional phenotype, supporting CD4 CTLs as a candidate blood-accessible biomarker for treatment stratification.

  单细胞
• Collagen-PMMA scaffolds induce dermal remodeling and immune recruitment distinct from simple volar fibroblast therapy in human skin [scRNAseq]
  GSE350894Homo sapiens3 个样本2026-10-31

  Cellular therapy is promising but requires optimization in human subjects. Volar skin of the palms and soles is adapted to mechanical stress through a thick epidermis and dense extracellular matrix, whereas non-volar skin is vulnerable at high-pressure sites such as prosthetic limb interfaces. Because volar fibroblasts can partially reprogram non-volar skin, we tested whether collagen/polymethyl methacrylate (PMMA) could enhance volar fibroblast therapy. Healthy volunteers received vehicle, scalp fibroblast, or volar fibroblast injections, with or without collagen/PMMA, into non-volar skin. Durometer, optical coherence tomography, histology, and transcriptomic analyses showed volar-like structural changes and activation of skin-development, keratinocyte-differentiation, extracellular-matrix, and morphogenesis pathways. Collagen/PMMA promoted fibroblast, immune, and endothelial cell accumulation, consistent with a scaffold-associated tissue response. These findings distinguish volar fibroblast–associated skin identity changes from collagen/PMMA-induced stromal remodeling with foreign body, inflammatory, and fibrotic/myofibroblast-associated features.

  单细胞
• Single-cell analysis reveals sex-specific ERβ regulation of neurovascular protection in the AppNL-G-F mouse model of Alzheimer’s disease
  GSE350656Mus musculus4 个样本2026-10-31

  Alzheimer’s disease (AD) exhibits pronounced sex differences, but the molecular mechanisms underlying this dimorphism remain unclear. To investigate the role of estrogen receptor beta (ERβ; Esr2) in modulating sex-specific amyloid pathology, single-cell RNA sequencing was performed on hippocampal tissue from six-month-old male and female AppNL-G-F and AppNL-G-F/Esr2KO mice. Loss of Esr2 induced sex-dependent alterations in amyloid burden, glial activation states, and endothelial-centered intercellular communication networks, with more pronounced transcriptomic remodeling in males. Transthyretin (Ttr) emerged as a strongly sex-modulated gene associated with increased amyloid pathology in male Esr2-deficient mice. These data provide a sex-stratified transcriptomic resource for understanding ERβ-dependent regulation of cellular programs in AD-related pathology

  单细胞
• KLF16 and SIN3A facilitate endometrial cancer cell proliferation in association with CTD-2377D24.6
  GSE349296Homo sapiens6 个样本2026-10-31

  Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Pathogenetically, most cases arise from uncontrolled proliferative expansion of endometrial cells under prolonged estrogen stimulation, ultimately leading to malignant transformation within the glandular epithelium. Identifying key regulators of aberrant endometrial proliferation is therefore critical for developing novel therapeutic modalities against EC. In the present study, we characterized Kruppel-like factor 16 (KLF16), a transcription factor that drives proliferative signaling across multiple cellular components of the endometrium, including endothelial, epithelial, and smooth muscle cell types. Clinicopathological analysis revealed significantly elevated KLF16 expression in human EC tissues, which was positively associated with both advanced tumor stages and high histological grades. Genetic perturbation experiments demonstrated that knockdown of KLF16 robustly inhibited endometrial cancer cell proliferation in vitro and impeded tumor growth in vivo. Given its role as a master regulator controlling broad transcriptomic programs encompassing both protein-coding genes and non-coding RNAs, we performed unbiased screening and identified lncRNA CTD-2377D24.6 as a potential downstream mediator associated with KLF16 signaling. Notably, overexpression of CTD-2377D24.6 effectively counteracted the anti-proliferative effects induced by KLF16 depletion. Mechanistically, single-cell transcriptomics, coimmunoprecipitation, and functional assays demonstrated that SIN3A interacts with KLF16 and may contribute to the association between KLF16 and CTD-2377D24.6 expression, which is linked to enhanced endometrial cancer cell proliferation. Together, these findings established KLF16 contributes to endometrial cancer progression and highlight the KLF16/SIN3A/CTD-2377D24.6-associated regulatory axis as a potential molecular pathway relevant to EC proliferation.

  单细胞扰动筛选
• HNRNPH2-R114W remodels RNA splicing and neurodevelopmental gene programs in isogenic cerebral organoids
  GSE348913Homo sapiens4 个样本2026-10-31

  Autism spectrum disorder has been linked to disrupted RNA processing during corticogenesis, yet variant-specific mechanisms remain difficult to resolve. Isogenic cerebral organoids derived from a patient-derived induced pluripotent stem cell (iPSC) line carrying the HNRNPH2-R114W variant and its CRISPR-corrected counterpart serve as a human developmental model to investigate variant-associated RNA dysregulation. Imaging quantification and exploratory bulk RNA sequencing, performed at a single developmental time point using one pooled organoid RNA sample from each genotype, identify coordinated remodeling of neuronal and metabolic programs, along with junction-centered splicing dysregulation involving 6,310 differentially used junctions. Computational structural docking situates HNRNPH2 RNA recognition motifs (RRMs) 1-3 within a spliceosomal context and locates residue R114 near a predicted RNA-contact interface, indicating that the R114W substitution may alter RNA engagement. Integration of differential expression with event- and isoform-level analyses identifies regulatory hubs enriched for axon guidance and synaptic signaling pathways. Single-cell-reference-based deconvolution suggests modest compositional shifts that are unlikely to account for the extent of transcriptional and splicing alterations observed. Collectively, these findings implicate HNRNPH2-R114W in widespread RNA rewiring and define candidate isoform-level endpoints for mechanistic and therapeutic investigation in human cortical organoids. These molecular signatures open new avenues to examine how HNRNPH2-associated RNA dysregulation evolves across developmental time and recurs across independent biological contexts, providing a foundation for further mechanistic studies of this rare neurodevelopmental disorder.

  单细胞计算与 AI
• Single-cell regulatory genomics reveals coordinated myeloid and T-cell reprogramming in liver cirrhosis
  GSE348509Homo sapiens6 个样本2026-10-31

  We performed single-cell RNA sequencing (scRNA-seq) on liver tissues from 3 cirrhotic patients and 3 non-cirrhotic controls, analyzing 43,745 high-quality cells. We investigated cellular composition, SCENIC regulon activity, pseudotime trajectories, and CellChat communication. Cirrhosis was associated with Mono1 depletion, expansion of inflammatory macrophages and regulatory T cells, dysregulated YY1/ETV6 regulons in myeloid cells, altered EOMES/KLF6 programs in cytotoxic T cells, and increased EP300/SP3 in Tregs, along with fibrosis-biased ligand-receptor signaling. Note: Raw sequencing data are not available because the sequencing company routinely clears data after two years; only processed expression matrices are provided.

  单细胞
• A Viral Replication Level-Dependent Continuum of Transcriptional and MicroRNA Reprogramming in HIV-1-Infected Microglia Links Productive Infection to Neurocognitive-Associated Gene Networks [RNA-seq]
  GSE341759Homo sapiens8 个样本2026-10-31

  Microglia are major targets of HIV-1 in the brain. Despite the effectiveness of antiviral therapy, infected microglia, including those containing a replication-defective provirus, can express viral RNA and proteins that contribute to neuroinflammation. However, the degree to which productive infection shapes the host response in microglia remains poorly defined. Using single cell RNA-seq of HIV-1-infected C20 microglia, we stratified cells by counts of HIV-1 reads with splice junctions into low- and high-infection groups, enabling us to resolve a graded rather than binary host transcriptional response. A core set of immune and cell-cycle pathways was induced regardless of infection level, but several programs reversed direction with increasing viral burden: interferon-α/γ and EMT/hypoxia signatures peaked at low infection, while high infection was marked by suppression of these signatures alongside induction of mTORC1/MYC signaling, ribosome biogenesis, RNA processing, and mitotic activity, accompanied by progressive loss of cytoskeletal, motility, and developmental gene programs. This pattern was reproduced in iPSC-derived microglia, supporting its generalizability beyond an immortalized line. Integration of differentially expressed miRNAs with differentially expressed genes from the low- and high-infection groups showing the canonical inverse miRNA-target relationship revealed miRNA/mRNA networks with strong representation of miRNAs previously implicated in HIV-1 replication (e.g., miR-33a-5p, miR-3065-3p) and in neurodegenerative and psychiatric disease (e.g., miR-107, let-7c-5p). These findings define a productive-infection-level continuum in microglial transcription, miRNA reprogramming, and identify candidate miRNA-mediated mechanisms, independent of the canonical Env/Nef/Tat pathway, by which HIV-1-infected microglia may contribute to neuroinflammation and neurocognitive impairment in people with HIV-1.

  单细胞
• A Viral Replication Level-Dependent Continuum of Transcriptional and MicroRNA Reprogramming in HIV-1-Infected Microglia Links Productive Infection to Neurocognitive-Associated Gene Networks [scRNA-seq]
  GSE341758Homo sapiens6 个样本2026-10-31

  Microglia are major targets of HIV-1 in the brain. Despite the effectiveness of antiviral therapy, infected microglia, including those containing a replication-defective provirus, can express viral RNA and proteins that contribute to neuroinflammation. However, the degree to which productive infection shapes the host response in microglia remains poorly defined. Using single cell RNA-seq of HIV-1-infected C20 microglia, we stratified cells by counts of HIV-1 reads with splice junctions into low- and high-infection groups, enabling us to resolve a graded rather than binary host transcriptional response. A core set of immune and cell-cycle pathways was induced regardless of infection level, but several programs reversed direction with increasing viral burden: interferon-α/γ and EMT/hypoxia signatures peaked at low infection, while high infection was marked by suppression of these signatures alongside induction of mTORC1/MYC signaling, ribosome biogenesis, RNA processing, and mitotic activity, accompanied by progressive loss of cytoskeletal, motility, and developmental gene programs. This pattern was reproduced in iPSC-derived microglia, supporting its generalizability beyond an immortalized line. Integration of differentially expressed miRNAs with differentially expressed genes from the low- and high-infection groups showing the canonical inverse miRNA-target relationship revealed miRNA/mRNA networks with strong representation of miRNAs previously implicated in HIV-1 replication (e.g., miR-33a-5p, miR-3065-3p) and in neurodegenerative and psychiatric disease (e.g., miR-107, let-7c-5p). These findings define a productive-infection-level continuum in microglial transcription, miRNA reprogramming, and identify candidate miRNA-mediated mechanisms, independent of the canonical Env/Nef/Tat pathway, by which HIV-1-infected microglia may contribute to neuroinflammation and neurocognitive impairment in people with HIV-1.

  单细胞
• A Viral Replication Level-Dependent Continuum of Transcriptional and MicroRNA Reprogramming in HIV-1-Infected Microglia Links Productive Infection to Neurocognitive-Associated Gene Networks [miRNA-seq]
  GSE341757Homo sapiens4 个样本2026-10-31

  Microglia are major targets of HIV-1 in the brain. Despite the effectiveness of antiviral therapy, infected microglia, including those containing a replication-defective provirus, can express viral RNA and proteins that contribute to neuroinflammation. However, the degree to which productive infection shapes the host response in microglia remains poorly defined. Using single cell RNA-seq of HIV-1-infected C20 microglia, we stratified cells by counts of HIV-1 reads with splice junctions into low- and high-infection groups, enabling us to resolve a graded rather than binary host transcriptional response. A core set of immune and cell-cycle pathways was induced regardless of infection level, but several programs reversed direction with increasing viral burden: interferon-α/γ and EMT/hypoxia signatures peaked at low infection, while high infection was marked by suppression of these signatures alongside induction of mTORC1/MYC signaling, ribosome biogenesis, RNA processing, and mitotic activity, accompanied by progressive loss of cytoskeletal, motility, and developmental gene programs. This pattern was reproduced in iPSC-derived microglia, supporting its generalizability beyond an immortalized line. Integration of differentially expressed miRNAs with differentially expressed genes from the low- and high-infection groups showing the canonical inverse miRNA-target relationship revealed miRNA/mRNA networks with strong representation of miRNAs previously implicated in HIV-1 replication (e.g., miR-33a-5p, miR-3065-3p) and in neurodegenerative and psychiatric disease (e.g., miR-107, let-7c-5p). These findings define a productive-infection-level continuum in microglial transcription, miRNA reprogramming, and identify candidate miRNA-mediated mechanisms, independent of the canonical Env/Nef/Tat pathway, by which HIV-1-infected microglia may contribute to neuroinflammation and neurocognitive impairment in people with HIV-1.

  单细胞
• GOLDEN: Gene expression and allele-informed decomposition for genetic heterogeneity in spatial transcriptomic data
  GSE341398Homo sapiens2 个样本2026-10-31

  Spatial transcriptomics (ST) enables exploration of cellular interactions, but current methods rely on pathologist annotation and face limitations in addressing genetic heterogeneity, where niches harbor non-clonal cells, as in placental or allograft tissues. To decipher such inter-individual heterogeneity in ST, we developed GOLDEN (Gene expression and allele-informed decomposition for genetic heterogeneity), an allele-aware multi-task network that encodes spot-level expression into shared latent representations. Incorporating allele features, it uses dual heads to classify spot identity (target, non-target, or mixed) and to estimate target fractions. For evaluation, we generated synthetic ST data via a Gamma-distribution model using semi-allogeneic single-cell profiles. On these synthetic benchmarks, GOLDEN achieved reliable deconvolution (Pearson's r = 0.977; MAE = 0.045) while maintaining consistent predictions across real-world STs, which were validated through genetic evidence.

  单细胞空间转录组计算与 AI
• Single cell transcriptomic sequencing in common mouse models of atherosclerosis
  GSE332811Mus musculus8 个样本2026-10-31

  A single cell analysis of mice aorta to perform comprehensive comparison among common mouse models of atherosclerosis

  单细胞
• Single-cell atlas reveals shared early microenvironmental remodeling in colorectal polypogenesis
  GSE327909Homo sapiens6 个样本2026-10-31

  Colorectal polyps are the earliest precancerous lesions in colorectal carcinogenesis, but their common microenvironmental drivers remain incompletely defined. We performed single-cell RNA sequencing on paired normal mucosal and colorectal polyp tissues from 3 patients with unselected lesions, including hyperplastic polyps and tubular adenomas. After quality control, 31,147 high-quality cells were obtained. Comparative analysis revealed four conserved hallmarks of colorectal polyps relative to normal mucosa: disrupted epithelial homeostasis characterized by stem cell expansion, Paneth cell reduction, and Wnt pathway activation; pro-inflammatory polarization of CD4+ T cells with increased Th17 cells and activation of NF-kB/IL-17-related pathways; functional reprogramming of CD8+ T cell subsets, especially decreased IELs with specialized immune functions; and extensive remodeling of immune-epithelial intercellular communication, including CD55-ADGRE5, MIF-CD74, and GZMA-PARD3 signaling axes. These data provide a single-cell atlas of shared microenvironmental changes in early colorectal polypogenesis.

  单细胞细胞图谱
• A Single-Cell Atlas of Human Periodontal Ligament During Orthodontic Tooth Movement
  GSE327337Homo sapiens5 个样本2026-10-31

  Orthodontic tooth movement (OTM) requires coordinated remodeling of the periodontal ligament (PDL) and alveolar bone, yet the cellular architecture underlying this process in human tissues remains incompletely understood. Here, we generated the first single-cell transcriptomic atlas of the human PDL during OTM by profiling cells from the pressure and tension sides of teeth collected at day 3 and day 7 following force application. This atlas reveals the major stromal and immune cell populations and highlights spatial and temporal heterogeneity across force conditions and remodeling stages.

  单细胞空间转录组细胞图谱
• Somatic TP53 Mutations Drive T and NK Cell Dysfunction and Create an Inflammatory Immune Niche in Acute Myeloid Leukemia
  GSE324592Homo sapiens2 个样本2026-10-31

  TP53-mutant acute myeloid leukemia (AML) is characterized by poor prognosis and limited response to immunotherapy, yet the mechanisms underlying immune failure in this setting remain unclear. Here, we integrate single-cell DNA sequencing with surface proteomics to demonstrate that somatic TP53 mutations arise not only in leukemic blasts but also in T and NK cells from patients with TP53-mutant AML. TP53-mutant T cells exhibit enhanced exhaustion phenotypes, impaired cytotoxic function, and altered clonal architecture. Mechanistically, mutant p53 reprograms T cells toward a pro-inflammatory yet dysfunctional state, reshaping cytokine networks and promoting a niche enriched in inflammatory and myeloid-supportive signals. These mutant T cells impair both intrinsic effector function and the functionality of surrounding immune cells. Introduction of TP53 mutations into healthy donor T cells recapitulates exhaustion and impaired tumor control, whereas elimination of mutant p53 restores effector function, normalizes cytokine programs, and improves disease control in a TP53-mutant AML xenograft model.

  单细胞
• Geometric inference of cross-species transcriptome correspondence [scRNA-Seq]
  GSE307645Macaca fascicularis; Pan troglodytes; Gorilla gorilla; Pongo abelii; Homo sapiens; Mus musculus6 个样本2026-10-31

  Sequence homology underpins cross-species analysis but cannot identify evolutionarily distinct genes that play analogous regulatory roles. Furthermore, ethical restrictions on human experiments necessitate analytical frameworks that translate insights from other animals to humans. To address these challenges, we develop Species-OT, a cross-species transcriptome analysis framework based on Gromov-Wasserstein optimal transport, which quantitatively compares the geometry of transcriptome distributions. Given a pair of bulk or single-cell RNA-sequencing datasets, Species-OT returns a gene-to-gene correspondence capturing probabilistic alignments of regulatory roles, and a transcriptomic distance quantifying overall divergence. Applied pair wise, Species-OT yields a transcriptomic discrepancy array and a hierarchical clustering tree analogous to a phylogenetic tree. We validate Species-OT using bulk RNA-seq data from human, mouse, and macaque germ cell specification as well as scRNA-seq data from pluripotent stem cells of six mammalian species. Species-OT identifies evolutionarily related and distinct gene correspondences including biologically unexplored candidates, while transcriptomic discrepancies recapitulate expected species relationships.

  单细胞
• Chronic Inflammatory Responses in Diabetic Lung and its’ Implications for Tuberculosis Infection.
  GSE280089Mus musculus8 个样本2026-10-31

  Diabetes mellitus (DM) increases (~3.11-fold) the risk of tuberculosis (TB), leading to worse disease outcomes and higher relapse rates. scRNAseq revealed compromised adaptive and innate immunity in DM-TB mice, with decreased Th1 and M1 macrophage populations. Further analysis showed hyperinflammation in DM and dampened immune responses in DM-TB, marked by increased IL-16 signaling and reduced TNF and IFN-II responses.

  单细胞
• StrataChip: a microphysiological system to capture dynamic keratinocyte fate and mechanical transitions during human epidermal morphogenesis
  GSE351999Homo sapiens1 个样本2026-10-30

  Epidermal development and homeostasis require precise coordination between keratinocyte differentiation and mechanics. Still, the mechanisms integrating these processes remain poorly understood in part due to limitations of existing experimental systems. Here, we introduce StrataChip, a tractable microphysiological system that enables dynamic, multimodal interrogation of human epidermal morphogenesis. The platform integrates a media perfused dermal tissue with human epidermal keratinocytes within a microfluidic device and supports rapid epidermal stratification following establishment of an air-liquid interface. High-resolution confocal imaging and single-cell RNA-sequencing demonstrate that the StrataChip recapitulates key architectural and molecular features of human epidermis, including distinct basal, spinous, and granular layers defined by canonical differentiation markers and adhesion molecule organization. Single-cell profiling reveals transcriptionally distinct basal and spinous subpopulations, including transitional states associated with suprabasal commitment. Live 3D imaging in situ captures keratinocyte morphodynamics including basal cell delamination and asymmetric division in early stages of epidermal stratification. Altogether, StrataChip provides a robust platform that is capable of dynamic and mechanistic interrogation of how gene regulation and cell mechanical changes are coupled during epidermal morphogenesis.

  单细胞
• Single-cell RNA sequencing of pooled orthotopic pancreatic tumors derived from PKM2-WT and PKM2-K89R cells
  GSE351631Mus musculus2 个样本2026-10-30

  We performed single-cell RNA sequencing of orthotopic pancreatic tumors established in NCG mice using pancreatic cancer cells expressing wild-type PKM2 (PKM2-WT) or the lactylation-deficient PKM2 K89R mutant (PKM2-K89R). For each group, tumor tissues from five mice were pooled before single-cell library preparation, resulting in one library per group. The dataset was used to characterize the tumor microenvironment and compare cell-type composition and cellular transcriptional states between the PKM2-WT and PKM2-K89R groups, with particular focus on fibroblast and cancer-associated fibroblast (CAF) subpopulations.

  单细胞
• A CD4-lineage erythro-myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation [scRNA-Seq]
  GSE345262Mus musculus3 个样本2026-10-30

  Tissue-resident macrophages originate from distinct developmental sources, but in adulthood, their replenishment is thought to depend exclusively on circulating monocytes. Here, we identify a previously unrecognized CD4-lineage erythro-myeloid progenitor, termed EMPROR (Erythro-Myeloid Progenitor), that resides in the adult bone marrow and defines an alternative pathway for generating macrophages. EMPROR cells are phenotypically and transcriptionally distinct from hematopoietic stem cells, common myeloid progenitors, and monocyte precursors. They lack expression of Csf1r and Ccr2 while expressing Cd4 and c-Kit. Single-cell RNA sequencing, RNA velocity analysis, and in vitro and in vivo lineage assays demonstrate a multilineage potential encompassing macrophage, neutrophil, megakaryocytic, and erythroid fates. In vivo, EMPROR cells efficiently generate perivascular and tumor-associated macrophages independently of CCR2-mediated monocyte recruitment, and also contribute to erythroid and granulocytic lineages under inflammatory and neoplastic conditions. Transcriptomic comparisons position EMPROR cells closest to embryonic erythro-myeloid progenitors, indicating that an embryonic-like erythro-myeloid program persists within the adult bone marrow. These findings expand current models of adult myelopoiesis and highlight a previously unappreciated developmental pathway that sustains macrophage diversity beyond the classical monocyte lineage.

  单细胞
• CRYAB-driven mitochondrial fission induces senescence to promote adaptive resistance to EGFR-TKI in LUAD brain metastasis
  GSE326531Mus musculus4 个样本2026-10-30

  Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) exhibit limited efficacy against lung cancer brain metastases, often resulting in rapid and inevitable resistance. However, the unique mechanisms driving this brain microenvironment-specific therapeutic failure remain elusive. Here, utilizing in vivo orthotopic models and single-cell RNA sequencing, we reveal that targeted therapy induces a distinct, metabolically hyperactive senescent cell subpopulation that drives rapid EGFR-TKI tolerance in brain metastasis. We identify the molecular chaperone CRYAB as an indispensable driver specifically upregulated within this senescent persister state. Mechanistically, CRYAB physically interacts with VDAC2 at the outer mitochondrial membrane, promoting endoplasmic reticulum (ER)-mitochondria tethering and calcium influx. This CRYAB-VDAC2 axis orchestrates adaptive mitochondrial fission, hyperactivating oxidative metabolism while simultaneously shielding（preventing？） senescent cells from fatal oxidative stress. Genetic or pharmacological blockade of mitochondrial fission completely abolishes CRYAB-mediated therapeutic resistance. Therapeutically, we demonstrate that a 25-hydroxycholesterol (25HC) dietary intervention acts as a potent in vivo senolytic strategy, directly dismantling the CRYAB-dependent resistance network, eradicating senescent persister cells, and synergistically prolonging overall survival when combined with Osi. Furthermore, high baseline CRYAB expression in pre-treatment primary lung biopsies clinically predicts lower intracranial objective response rates and shorter progression-free survival in a cohort of advanced EGFR-mutant NSCLC patients. Collectively, our study uncovers a novel CRYAB-VDAC2-mitochondrial fission axis that enforces therapy-induced senescence and highlights 25HC dietary intervention as a highly translatable combinatorial strategy to overcome EGFR-TKI resistance in brain metastasis.

  单细胞
• A Cross-scale Causal Mapping Framework Pinpoints Macrophage Orchestrators of Balanced Arterial Development
  GSE317047Homo sapiens3 个样本2026-10-30

  This dataset contains single-cell RNA sequencing profiles of induced pluripotent stem cell (iPSC)-derived blood vessel organoids (BVOs) cultured under different macrophage co-culture conditions. The aim is to investigate the regulation of vascular maturation and arterial development by the immune system. The BVOs were cultured either alone or with two polarized populations of iPSC-derived macrophages: activated (MGL low) and regenerative (MGL high). Single-cell transcriptomic analyses revealed polarization-dependent transcriptional changes in vascular endothelial and perivascular cell populations. This dataset allows for the identification of candidate genes and signaling pathways associated with arterial specification, vessel stabilization, and vascular maturation in a human organoid model.

  单细胞
• scRNAseq analysis of rat dorsal root ganglions from different peripheral injury treatment; a nerve transection, a crush 2 weeks after the cut and a resection of the neuroma 2 weeks afrer the initial cut
  GSE315353Rattus norvegicus6 个样本2026-10-30

  Peripheral nerve injury, whether caused by a cut, crush, or excessive stretch, can result in the formation of a painful neuroma at the site of damage. After a traumatic injury, regenerating nerves may develop a painful swelling at the severed end. This development is often accompanied by significant pain along the affected nerve's distribution, which can, in some cases, be more debilitating than the loss of motor function or sensation. It has been hypothesized that a proximal nerve crush may offer therapeutic benefits for painful neuromas by altering the axonal growth pattern and disrupting retrograde signaling. Despite existing treatment approaches, success in managing neuromas has been limited. Therefore, it is crucial to deepen our understanding of painful neuromas and develop more effective therapies. The molecular mechanisms underlying the formation and pain associated with symptomatic neuromas remain poorly understood. In this study, we thoroughly characterize the transcriptional changes in the dorsal root ganglion at single-cell resolution following proximal nerve crush versus nerve resection after neuronal transection.

  单细胞
• Immune cells adapt to distinct stem cell niches to govern tissue homeostasis [scRNA-seq]
  GSE314679Mus musculus2 个样本2026-10-30

  In adult tissues, epithelial stem cells exist within distinct residences, each endowing them with exclusive instructions for regenerative fitness in homeostasis and wound repair. Key components of these ‘niches’ are immune cells, which protect the host against external and internal threats. Whether and how stem cell: immune cell crosstalk contributes to normal tissue homeostasis remains less clear. Here, we discover functional adaptation of lymphocytes within two distinct skin stem cell niches and show that through this communication, each niche adjusts to meet diverse tissue demands. In the upper hair follicle, where microbial load is high, T cells express lymphotoxin-β and stimulate adjacent receptor-positive epithelial stem cells to form an immune-competent niche tailored to control microbial expansion. By contrast, in the epidermis, these T cells produce amphiregulin to maintain stem cell stoking of the skin’s barrier. Concomitantly, they express the immune checkpoint protein ‘LAG3’, which autorestricts lymphocyte numbers, and hence amphiregulin levels, thereby preventing over-proliferative responses. Finally, when epidermal T cells are absent, distinct dermal lymphocytes restore the imbalance by colonizing the niche and activating amphiregulin. Our findings unveil new modes of homeostatic control and functional specialization of immune-stem cell niches, tailoring them to suit the demands of distinct tissue microenvironments.

  单细胞
• Multi-lineage evolution of drug resistance via a keratin 17+ aberrant basaloid drug tolerant persister population in EGFR-mutant NSCLC
  GSE303284Homo sapiens6 个样本2026-10-30

  We have an incomplete understanding of how EGFR-mutant drug tolerant persister cells (DTPCs) adapt to tolerate EGFR signaling blockade and whether these different mechanisms of resistance are present at baseline or emerge from a common DTPC population. In this study, we leveraged single cell RNA sequencing to comprehensively characterize phenotypes potentiating EGFR-mutant DTPCs and minimal residual disease states in part by sampling in vitro model systems. Using this and other single cell RNA sequencing data, we uncovered that a recurrent, novel KRT17+/KRT5- DTPC population harboring basaloid features and decreased alveolar lineage fidelity could give rise to diverse, multilineage mechanisms of targeted therapy resistance.

  单细胞
• Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigration [scATAC-seq]
  GSE297937Mus musculus2 个样本2026-10-30

  T cell development progresses through discrete stages that require precise control of gene activation and gene repression. Gene silencing is primarily mediated through epigenetic modifications, mediated by the interaction of transcription factors with repressor complexes containing chromatin-remodeling enzymes. Found within many such complexes, the corepressors NCOR1 and NCOR2 recruit histone deacetylases to suppress transcription of target genes. Using Cd4-cre mice, we identified multiple roles for NCOR1 and NCOR2 throughout thymocyte development. Here, we employed scATAC-seq to examine whether the RNA- and protein-level differences observed in these mice correlate with changes in chromatin accessibility.

  单细胞
• Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigration
  GSE246149Mus musculus3 个样本2026-10-30

  T cell development proceeds via discrete stages that require both gene induction and gene repression. Transcription factors direct gene repression by associating with corepressor complexes containing chromatin-remodeling enzymes; the corepressors NCOR1 and NCOR2 recruit histone deacetylases to these complexes to silence transcription of target genes. Earlier work identified the importance of NCOR1 in promoting the survival of positively-selected thymocytes. Here, we used flow cytometry and single cell RNA sequencing to identify a broader role for NCOR1 and NCOR2 in regulating thymocyte development. Using Cd4-cre mice, we found that conditional deletion of NCOR2 had no effect on thymocyte development, whereas conditional deletion of NCOR1 had a modest effect. In contrast, Cd4-cre x Ncor1f/f x Ncor2f/f mice exhibited a significant block in thymocyte development at the DP to SP transition. Combined NCOR1/2 deletion resulted in increased signaling through the T cell receptor, ultimately resulting in elevated BIM expression and increased negative selection. The NF-κB, NUR77, and MAPK signaling pathways were also upregulated in the absence of NCOR1/2, contributing to altered CD4/CD8 lineage commitment, TCR rearrangement, and thymocyte emigration. Taken together, our data identify multiple critical roles for NCOR1/2 throughout thymocyte development.

  单细胞
• SH2 Domain Protein E sustains perivascular fibroblasts to maintain arterial stability
  GSE352057Danio rerio8 个样本2026-10-29

  Developing arteries must withstand pulsatile blood flow while remaining sufficiently flexible to accommodate changing hemodynamic demands. Endothelial interactions with perivascular cells and extracellular matrix are essential for this balance, but the signaling mechanisms that coordinate them remain incompletely understood. We previously showed that SH2 domain protein E (She), an endothelial adaptor protein implicated in ABL signaling, limits the size of the dorsal aorta (DA) in zebrafish embryos. Here, we investigated why zebrafish she mutants subsequently develop DA collapse and circulatory failure at 4–5 days post-fertilization. Before circulatory failure, the mutant DA retained an approximately circular cross-section and showed no detectable changes in the endothelial cell geometry, but exhibited increased distensibility during the cardiac cycle. Mutants had fewer perivascular stromal cells between the DA and posterior cardinal vein, smaller perivascular col1a1 and col5a1 expression domains, and reduced col1a1 transcript level. Single-cell RNA sequencing independently identified a reduced relative abundance of perivascular fibroblast subpopulation. In contrast, DA-associated mural cell numbers, laminin immunoreactivity, and local col4a1 transcript levels were not detectably altered. Ablation of pdgfrb-positive cells largely prevented DA narrowing and circulatory failure, while the nitric oxide donor sodium nitroprusside provided partial rescue. These findings support a contribution of mural cell-dependent vascular tone to collapse of the mechanically vulnerable DA. Mutants also exhibited cardiac chamber enlargement, increased atrial and bulbus arteriosus deformation, atrioventricular regurgitation, and increased Elastin B accumulation in the enlarged bulbus arteriosus. However, endocardial-specific She expression failed to rescue circulatory failure, supporting its requirement in vascular endothelium. Together, these findings link She function to perivascular fibroblast abundance, fibrillar collagen-gene expression, and arterial stability. They support a model in which impaired perivascular support renders the developing DA susceptible to mural cell-associated collapse, extending the role of She from early vessel-size regulation to maintenance of vascular function.

  单细胞
• Transcriptional response of primary human pancreatic cancer-associated fibroblasts to IFN-γ and lipopolysaccharide stimulation
  GSE348821Homo sapiens9 个样本2026-10-29

  Single-cell analysis of a pan-cancer tumor microenvironment atlas identified transcriptionally distinct inflammatory cancer-associated fibroblast (iCAF) subpopulations, including an ISG15+ iCAF population predicted to arise downstream of interferon-γ signaling from CD8+/GZMB+ T cells, and a CXCL8+ iCAF population. To test these predictions experimentally, primary cancer-associated fibroblasts (CAFs) were isolated from a fresh human pancreatic ductal adenocarcinoma (PDAC) surgical specimen, expanded in culture, and treated for 24 hours with control media, recombinant human interferon-γ, or lipopolysaccharide (LPS). Bulk RNA-sequencing of the resulting nine libraries was used to compare the induced transcriptional programs against gene signatures derived from the ISG15+ iCAF and CXCL8+ iCAF subpopulations of the atlas. Results are reported in the associated publication.

  单细胞细胞图谱
• Prenatal maternal cold stress exposure drives sex-specific neurodevelopmental disruptions in the fetal hypothalamus
  GSE328919Mus musculus3 个样本2026-10-29

  The prevalence of neurodevelopmental disorders (NDDs) is increasing, with growing evidence implicating the intrauterine environment as a critical regulator of fetal brain development. Gestational perturbations such as maternal stress can increase NDD risk; however, the mechanism(s) by which prenatal maternal stress reshape fetal neurodevelopment remain unclear. Accordingly, the objective of my project was to characterize how maternal cold stress exposure during pregnancy disrupts neural stem and progenitor cell (NSPC) developmental programs in the fetus and the impact this has on neurodevelopment in the hypothalamus. Pregnant mice were exposed to 4°C for 30 minutes daily from embryonic day 11.5 (E11.5) to E15.5—a critical period of neurodevelopment in the hypothalamus. To assess how maternal cold stress impacts neural stem cell (NSC) behaviours, we employed the neurosphere assay, quantifying the number and size of primary and secondary neurospheres as a measure of NSC proliferation and self-renewal, respectively. Our findings revealed no change in NSC proliferation or self-renewal when comparing control and maternal cold stress male and female neurospheres. However, differentiation of dissociated NSCs revealed that neurons from both sexes had longer axons following maternal cold stress exposure. Interestingly, only male-derived cultures exhibited a significant increase in the number TUJ1+ neurons in response to maternal cold stress exposure, whereas only female-derived maternal cold stress cultures showed enhanced dendritic arborization. To explore the molecular basis of these changes, we performed single-cell RNA sequencing on E15.5 fetal hypothalamic NSPCs. Analysis of differentially expressed genes uncovered basal sex differences between the transcriptional signatures of control male and female Cycling NSPCs and suggested that maternal cold stress shifts female Cycling NSPCs toward a more male-like transcriptional profile. Gene ontology analysis revealed that maternal cold stress upregulates pathways linked to neuronal growth, development, and GABAergic neuron differentiation, but only in females. Importantly, ligand-receptor analysis suggested that maternal cold stress exposure disrupts neurodevelopmental programs through altered cell-cell signalling within Cycling NSPCs predominantly in females. These findings demonstrate that prenatal maternal cold stress exposure drives sex-specific effects on fetal neurodevelopment and uncover distinct cellular pathways that may contribute to sex differences seen in the presentation and risk of many NDDs.

  单细胞扰动筛选