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。

• Sleep-dependent DNA methylation remodeling in basolateral amygdala fear engrams [PIP-Seq]
  GSE348705Mus musculus16 个样本2026-10-31

  How memory consolidates via DNA methylation mechanisms during sleep in the basolateral amygdala (BLA), a critical brain region for fear memory, remains unknown. We performed whole-genome bisulfite sequencing (WGBS) on fear conditioning (FC)-activated cells from the BLAs of adult male mice experiencing either sleep or sleep deprivation following FC learning, evaluated at Day 7 and Day 28 timepoints. Additionally, Day 7 samples include paired single-nucleus RNA sequencing (snRNA-seq) using PIPseq technology. This dataset enables the integration of multi-omics (methylome and transcriptome) to understand learning-induced epigenomic programming in the BLA.

  单细胞多组学
• Targeting ERO1α Triggers Tumor Immunosurveillance in Triple-Negative Breast Cancer [scRNA-seq]
  GSE336881Mus musculus12 个样本2026-10-31

  Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited responsiveness to immune checkpoint blockade. Here, we identify endoplasmic reticulum oxidoreductase 1 alpha, a key regulator of oxidative protein folding, as a determinant of tumor immunogenicity and immunotherapy response in TNBC. Unbiased proteomic profiling demonstrated that ERO1α deficiency remodels the TNBC glycoproteome, leading to enrichment of pathways associated with innate immune signaling. Although ERO1α loss did not affect tumor cell growth, it reshaped the immune tumor microenvironment, enhancing antigen presentation, altering myeloid-cell composition, and modulating PD-1/PD-L1–associated signaling. Functionally, ERO1α deficiency sensitized otherwise refractory TNBC tumors to PD-1 blockade, resulting in durable tumor regression in immunocompetent hosts. In contrast, ERO1α deletion in bone marrow–derived immune cells had minimal effects on tumor growth or therapeutic response, supporting an ERO1α tumor-intrinsic mechanism. Pharmacologic inhibition of ERO1α with the novel small-molecule inhibitor I29 phenocopied ERO1α genetic deletion and enhanced the efficacy of anti–PD-1 therapy. Together, these findings identify ERO1α-dependent glycoproteome remodeling as a regulator of antitumor immunity and a therapeutically actionable mechanism of immune checkpoint responsiveness in TNBC.

  单细胞
• Sarm1 Gates the Transition from Protective to Repair Schwann Cell States Following Nerve Injury [snRNA-Seq]
  GSE332913Mus musculus11 个样本2026-10-31

  Schwann cells (SCs) transition into a Repair state after peripheral nerve injury; however, the early SC injury response preceding this transition remains poorly understood. We demonstrate that Sarm1, a key regulator of axon degeneration, is expressed and upregulated in SCs after nerve injury. Cell-type-specific Sarm1 knockout SCs exhibit enhanced axon protection in vitro, and SC- and glia-specific Sarm1 deletion confers axon protection in mouse sciatic nerve and Drosophila wing injury models. Single-nucleus RNA sequencing revealed that Sarm1-deficient SCs are enriched in a distinct cluster expressing genes with developmental roles in axon and myelin protection, with increased oxidative phosphorylation gene expression across all injured SC states. We propose that Sarm1 gates the transition from a Protection-Associated Schwann Cell (PASC) state to a Repair SC state, establishing Sarm1 as a multi-functional regulator with implications for peripheral neuropathies and neurodegenerative diseases.

  单细胞
• Sarm1 Gates the Transition from Protective to Repair Schwann Cell States Following Nerve Injury [RNA-seq]
  GSE332854Mus musculus12 个样本2026-10-31

  Schwann cells (SCs) transition into a Repair state after peripheral nerve injury; however, the early SC injury response preceding this transition remains poorly understood. We demonstrate that Sarm1, a key regulator of axon degeneration, is expressed and upregulated in SCs after nerve injury. Cell-type-specific Sarm1 knockout SCs exhibit enhanced axon protection in vitro, and SC- and glia-specific Sarm1 deletion confers axon protection in mouse sciatic nerve and Drosophila wing injury models. Single-nucleus RNA sequencing revealed that Sarm1-deficient SCs are enriched in a distinct cluster expressing genes with developmental roles in axon and myelin protection, with increased oxidative phosphorylation gene expression across all injured SC states. We propose that Sarm1 gates the transition from a Protection-Associated Schwann Cell (PASC) state to a Repair SC state, establishing Sarm1 as a multi-functional regulator with implications for peripheral neuropathies and neurodegenerative diseases.

  单细胞
• A CD4-lineage erythro-myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation [RNA-Seq]
  GSE345263Mus musculus10 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
• A CD4-lineage erythro-myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation
  GSE345108Mus musculus12 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
• CAR-DC1s drive polyclonal neoantigen-specific immunity
  GSE319838Mus musculus16 个样本2026-10-30

  CAR therapies typically target single antigens, limiting recognition and favoring tumour escape. Conversely, type 1 conventional dendritic cells (DC1s) are specialized to cross-prime diverse T-cell responses, but lack the pathogen-derived signals required for strong activation in "self"-derived tumors. Efforts to hard-wire such signals using CARs in DC1s have remained elusive, in part due to a lineage-specific constraint on stable, high-level CAR surface expression. Here, we show that replacing conventional antibody fragments with single-domain nanobodies overcomes this DC1–specific constraint and enables construction of tumour-targeted receptors with high surface density. By systematically optimizing TLR4-derived elements within this scaffold, we developed a receptor that couples tumor engagement to TLR signaling, markedly enhancing activation, capture and cross-presentation of endogenous antigens. In a heterogeneous syngeneic sarcoma model, CAR-DC1s induce complete tumor rejection and durable memory. Integrating mass spectrometry of the cross-presented tumour immunopeptidome with tetramer staining, single-cell RNA sequencing paired with TCR sequencing, and adoptive transfer, we show that CAR-DC1s imprint a stem-like transcriptional programme on newly primed T-cells and expand a polyclonal, recall-competent tumour-specific repertoire, thereby reprogramming the quality and breadth of anti-tumour immunity against endogenous neoantigen in vivo.

  单细胞
• 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
• 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
• 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
• 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