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
• 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
• 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 [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
• 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
• 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
• 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
• 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
  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
• 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
• 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