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 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
• 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
• 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
• Microglia modulate concussion biomarkers and recovery in male mice
  GSE330926Mus musculus55 个样本2026-10-31

  There is a critical unmet need for concussion biomarkers that predict cognitive recovery. Existing TBI biomarkers largely capture acute cellular damage rather than the multicellular repair processes that determine long-term outcome, and whether microglia causally shape divergent trajectories remains unclear. Here, we used PLX5622 to deplete microglia and other CSF1R-dependent myeloid cells in a male mouse model comparing concussion alone to concussion preconditioned by prior subconcussive impacts. Microglial depletion had no effect on cognitive outcome after concussion alone, but introduced a significant novel object recognition deficit specifically when concussion was preconditioned, revealing a history-dependent role for microglia in recovery. To identify the molecular substrates of this divergence, we profiled brain-derived GluA1/2 + extracellular vesicle (EV) miRNAs and single-nuclei transcriptomes from the injured brain. Diagnostic and injury-history EV miRNA biomarkers discriminated between concussion subtypes in microglia-intact animals but lost this discriminative power after depletion, indicating that these neuron-enriched biomarkers are influenced by microglia-dependent biology rather than injury alone. snRNA-seq further revealed that microglial depletion selectively induced transcriptional programs related to oligodendrocyte maturation after unconditioned concussion, a candidate substrate for this microglia-dependence. Finally, we identified a serum EV miRNA panel that estimated cognitive recovery across injury conditions. Together, these findings identify a history-dependent role for microglia in concussion outcome and characterize brain-derived EVs as a potentially promising tool for surveilling the neuroinflammatory processes influencing recovery.

  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
• 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 [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 [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
• 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
• 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
• 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
• 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
• 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
• 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
• Spatially resolved heterogeneity of lymphatic vasculature in the adult lung
  GSE325297Mus musculus2 个样本2026-10-29

  Background. Lung lymphatic drainage of interstitial fluid is essential for preventing pulmonary edema, a condition characterized by the accumulation of extravascular fluid that impedes respiratory gas exchange and can be fatal. Beyond fluid regulation, lung lymphatics also serve as conduits for immune cell trafficking, supporting both surveillance and mounting of host immune responses during lung infection. Despite their essential roles, the cellular and functional heterogeneity of lung lymphatic endothelial cells (LECs) remains poorly defined. Methods. Leveraging single nucleus sequencing technology, we investigated LEC heterogeneity in the homeostatic adult mouse lung. Results. We identified Stabilin-2 (Stab2), a Class H scavenger receptor, as a unique marker of a distinct subset of LECs in lymphatic vessels adjacent to pulmonary veins and in alveolar regions. A separate distinct subset of LECs is defined by expression of Polycystic Kidney and Hepatic Disease 1-Like-1 (Pkhd1l1), a component of stereocilia, and these lymphatic vessels are localized to the bronchovascular bundle. Conclusions. Our findings suggest that lung LECs are not a uniform population but instead compromise molecularly distinct and spatially organized lymphatic vessels, possibly with specialized functions. These results lay the groundwork for further studies geared towards understanding the roles of cellular origin in lung LEC heterogeneity, whether lymphatics in other organs have analogous spatial organization, and whether these disparate cells and vessels have functional differences in fluid homeostasis and immune regulation during pulmonary disease pathogenesis.

  单细胞空间转录组
• Two-phase NEUROD1 pioneer activity regulates temporal differentiation and subtype specification of auditory neurons [scRNA-Seq]
  GSE317781Mus musculus2 个样本2026-10-29

  The transcriptional and epigenetic mechanisms that govern neuronal subtype differentiation and diversification remain poorly defined, with auditory neurons among the least understood. Here, we investigate the role of the proneural factor NEUROD1 using a delayed, self terminating conditional knockout (Neurod1ST) mouse model that bypasses the early neuronal loss observed in germline mutants. By integrating NEUROD1 chromatin binding and histone profiling at E11.5 with transcriptomic analyses at E11.5, E14.5, and E18.5, we show that NEUROD1 is essential for coordinating the timing of neuronal differentiation. Neurod1 deletion prolongs progenitor-like states while prematurely accelerating differentiation and axonogenesis programs, reflecting the collapse of NEUROD1-dependent transcriptional networks and recruitment of compensatory pathways. NEUROD1 preferentially binds enhancers of neuronal differentiation genes and promotes their transition to active chromatin states, consistent with a pioneer factor function. Loss of Neurod1 disrupts these epigenomic transitions, alters neuronal migration and innervation trajectories, and ultimately leads to neuronal instability and apoptosis. During spiral ganglion neuron diversification, Neurod1ST neurons prematurely activate maturation markers and fail to generate Type Ic, instead adopting a Type Ib-like identity. These findings establish NEUROD1 as a central regulator that synchronizes differentiation, stabilizes neuronal identity, and shapes auditory neuron subtype diversity in the developing inner ear

  单细胞
• Two-phase NEUROD1 pioneer activity regulates temporal differentiation and subtype specification of auditory neurons [snRNA-Seq]
  GSE315741Mus musculus2 个样本2026-10-29

  The transcriptional and epigenetic mechanisms that govern neuronal subtype differentiation and diversification remain poorly defined, with auditory neurons among the least understood. Here, we investigate the role of the proneural factor NEUROD1 using a delayed, self terminating conditional knockout (Neurod1ST) mouse model that bypasses the early neuronal loss observed in germline mutants. By integrating NEUROD1 chromatin binding and histone profiling at E11.5 with transcriptomic analyses at E11.5, E14.5, and E18.5, we show that NEUROD1 is essential for coordinating the timing of neuronal differentiation. Neurod1 deletion prolongs progenitor-like states while prematurely accelerating differentiation and axonogenesis programs, reflecting the collapse of NEUROD1-dependent transcriptional networks and recruitment of compensatory pathways. NEUROD1 preferentially binds enhancers of neuronal differentiation genes and promotes their transition to active chromatin states, consistent with a pioneer factor function. Loss of Neurod1 disrupts these epigenomic transitions, alters neuronal migration and innervation trajectories, and ultimately leads to neuronal instability and apoptosis. During spiral ganglion neuron diversification, Neurod1ST neurons prematurely activate maturation markers and fail to generate Type Ic, instead adopting a Type Ib-like identity. These findings establish NEUROD1 as a central regulator that synchronizes differentiation, stabilizes neuronal identity, and shapes auditory neuron subtype diversity in the developing inner ear

  单细胞
• Two-phase NEUROD1 pioneer activity regulates temporal differentiation and subtype specification of auditory neurons [scRNAseq_E115]
  GSE315597Mus musculus2 个样本2026-10-29

  The transcriptional and epigenetic mechanisms that govern neuronal subtype differentiation and diversification remain poorly defined, with auditory neurons among the least understood. Here, we investigate the role of the proneural factor NEUROD1 using a delayed, self terminating conditional knockout (Neurod1ST) mouse model that bypasses the early neuronal loss observed in germline mutants. By integrating NEUROD1 chromatin binding and histone profiling at E11.5 with transcriptomic analyses at E11.5, E14.5, and E18.5, we show that NEUROD1 is essential for coordinating the timing of neuronal differentiation. Neurod1 deletion prolongs progenitor-like states while prematurely accelerating differentiation and axonogenesis programs, reflecting the collapse of NEUROD1-dependent transcriptional networks and recruitment of compensatory pathways. NEUROD1 preferentially binds enhancers of neuronal differentiation genes and promotes their transition to active chromatin states, consistent with a pioneer factor function. Loss of Neurod1 disrupts these epigenomic transitions, alters neuronal migration and innervation trajectories, and ultimately leads to neuronal instability and apoptosis. During spiral ganglion neuron diversification, Neurod1ST neurons prematurely activate maturation markers and fail to generate Type Ic, instead adopting a Type Ib-like identity. These findings establish NEUROD1 as a central regulator that synchronizes differentiation, stabilizes neuronal identity, and shapes auditory neuron subtype diversity in the developing inner ear

  单细胞
• Single-cell Characterization of DNA Hydroxymethylation of the Mouse Brain
  GSE314268Mus musculus1,449 个样本2026-10-29

  This SuperSeries is composed of the SubSeries listed below.

  单细胞SuperSeries
• Single-cell Characterization of DNA Hydroxymethylation of the Mouse Brain [scRNA-seq]
  GSE314217Mus musculus491 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
• Single-cell Characterization of DNA Hydroxymethylation of the Mouse Brain [5mC]
  GSE314211Mus 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
• 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
• 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
• 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