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。

• 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
• 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
• 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
• 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
• 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
• 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
• TNFR2 agonism increases tissue and effector Treg cells
  GSE344625Mus musculus2 个样本2026-10-26

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

  单细胞
• Attenuation of DOK3 re-programs tumor-associated macrophages to enhance anti-PD-1-mediated cancer immunotherapy [scRNA-seq MC38]
  GSE341712Mus musculus12 个样本2026-10-26

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

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

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

  单细胞
• Oxidative Stress Potentiates a STAT1–APOL1 Feedforward Loop and Governs Disease Severity in APOL1-Mediated Kidney Disease [Xenium]
  GSE334605Mus musculus2 个样本2026-10-26

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

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

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

  单细胞空间转录组
• The nail mesenchyme creates a regeneration-specific ligand environment that orchestrates mammalian regeneration versus fibrotic wound healing
  GSE326776Mus musculus98 个样本2026-10-26

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

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

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

  单细胞
• IGF2 regulates postnatal adipocyte progenitor proliferation and differentiation
  GSE309372Mus musculus2 个样本2026-10-26

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

  单细胞
• Oxidative Stress Potentiates a STAT1–APOL1 Feedforward Loop and Governs Disease Severity in APOL1-Mediated Kidney Disease
  GSE300326Mus musculus8 个样本2026-10-26

  Introduction: Apolipoprotein L1 (APOL1) risk variants (G1 and G2) confer immunity against Trypanosoma infection but markedly increase susceptibility to progressive kidney disease. However, only a subset of biallelic risk-variant carriers develops disease progression, distinct from murine models. Here, we evaluated molecular drivers of progressive disease using a model that reflected the low human disease penetrance. Methods: To investigate the heterogeneity of APOL1-mediated kidney disease, we generated novel APOL1 bacterial artificial chromosome transgenic mice with doxycycline-inducible systemic IFNγ expression (G0- or G1-IFNγ mice). Podocyte-specific transcriptomics using translating ribosome affinity purification (TRAP-seq) and single-cell spatial transcriptomics via 10x Genomics Xenium In Situ platform were performed. Mechanistic validation and analysis of factors regulating APOL1 upregulation were conducted in primary podocytes and subsequently validated in human and mouse kidney biopsy specimens via immunofluorescence. Results: A subset of G1-IFNγ mice developed severe albuminuria and focal segmental glomerulosclerosis, which strongly correlated with the magnitude of APOL1 upregulation. By pairing TRAP-seq with single-cell spatial transcriptomic data, we identified mitochondrial dysfunction and JAK-STAT signaling as a central mediator of podocyte injury. In primary podocytes, APOL1 risk variants triggered mitochondrial-derived oxidative stress, establishing a self-amplifying STAT1-APOL1 feedforward loop that further enhances APOL1 expression and APOL1 oligomerization. This pathogenic loop was consistently enriched in podocytes from both G1-IFNγ mice and in kidney biopsy specimens from patients with APOL1-mediated focal segmental glomerulosclerosis, demonstrating translational relevance. Conclusions: Our findings suggest that biallelic risk variants initiate an oxidative stress-induced positive feedback loop which promotes APOL1 upregulation and STAT1 phosphorylation, thereby contributing to disease susceptibility and outcome.

  单细胞空间转录组