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。

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

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

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

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

  单细胞
• Hyperglycemia drives an activated, lipid-laden non-classical monocyte phenotype in diabetes
  GSE339503Mus musculus36 个样本2026-10-26

  The presence of lipid-loaded macrophages in the artery wall and kidney characterizes diabetic atherosclerotic cardiovascular disease and diabetic kidney disease, respectively. Monocytes, the bone marrow-derived precursors of macrophages, accumulate lipids in response to hypercholesterolemia; however, whether diabetes directly alters monocyte lipid loading remains unclear. Using unbiased proteomics, we show that diabetes profoundly affects circulating monocytes, leading to upregulation of glucose metabolism pathways and suppression of cholesterol homeostasis pathways, indicative of lipid loading, particularly in non-classical monocytes. Functional analyses confirmed that non-classical monocytes exhibit increased glucose uptake and a lipid-loaded phenotype in three distinct mouse models of diabetes, and that they are also more lipid-loaded in people living with diabetes. The increased lipid loading of non-classical monocytes was not only due to dyslipidemia but to elevated glucose levels. Finally, we find that non-classical monocytes traffic to the kidney and contribute to a foamy population of kidney macrophages in a mouse model of diabetes. Together, these findings suggest that hyperglycemia in diabetes drives the reprogramming of non-classical monocytes, leading to lipid loading and the accumulation of lipid-loaded macrophages in the kidney.
• 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
• Preconception Paternal PFAS Exposure Reprograms the Placental Epigenome
  GSE333805Mus musculus28 个样本2026-10-26

  The placenta plays a vital role in supporting fetal growth and development by facilitating nutrient exchange, hormone signalling and immune regulation. Environmental toxicants such as perfluoroalkyl and polyfluoroalkyl substances (PFAS) can disrupt placental homeostasis, leading to increased risk of disease later in life. Paternal environmental exposures may influence offspring health by inducing epigenetic changes in sperm, which may affect sex-dependent placental programming. Here, male mice were exposed to a PFAS mixture (PFOS, PFOA, PFNA, PFHxS, GenX; 20 μg/L each) for 10 weeks and mated with unexposed females. We identified 6,656 and 3,242 differentially methylated regions (DMRs) in E12.5 placentas of female and male offspring, respectively. Female placentas showed predominantly hypermethylation (78.5%), whereas male placentas were mostly hypomethylated (62%). Gene ontology analyses linked female placental DMRs to cell and embryonic morphogenesis, and male DMRs to anatomical size regulation and hemostasis. Bulk RNA sequencing revealed 168 and 148 differentially expressed genes (DEGs) in female and male placentas, respectively. Female DEGs were related to immune regulation, while male DEGs were involved in muscle and mesenchyme development. Sex-by-PFAS interaction models identified distinct methylation and transcription biological pathways. Overlap analysis between F0 sperm and F1 placentas identified 265 shared genes, including 289 female-specific and 124 male-specific genes. Paternal exposure to the PFAS mixture increased glycogen concentrations in male, but not female, placentas. No effects were observed at imprinted loci. These findings demonstrate that paternal preconception exposure to a PFAS mixture alter placental epigenomic and transcriptomic landscapes, which may contribute to sex-dependent trajectories of fetal health and development and offspring phenotypes.
• The nail mesenchyme creates a regeneration-specific ligand environment that orchestrates mammalian regeneration versus fibrotic wound healing [scRNA-seq]
  GSE326786Mus musculus4 个样本2026-10-26

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

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

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

  单细胞空间转录组
• RNA Polymerase II Dynamics in Antiviral NK Cell Responses [Histone ChIP-Seq]
  GSE326752Mus musculus26 个样本2026-10-26

  Natural killer (NK) cells are innate lymphocytes that uniquely exhibit both innate and adaptive responses towards certain pathogens. During cytomegalovirus (CMV) infection, antigen-specific NK cells will generate a long-lived pool of memory cells with enhanced responses to secondary infection. The underlying molecular mechanisms that regulate early innate effector functions and delayed adaptive proliferation followed by longevity during antiviral NK cell differentiation remain to be fully understood. Here, we investigated the dynamics of serine-5 phosphorylated RNA Polymerase II (Pol IIS5P) occupancy in NK cells ex vivo during mouse CMV (MCMV) infection. During the initial NK cell antiviral response, Pol IIS5P occupancy increased broadly across the genome, at both upregulated and downregulated genes relative to NK cells at rest. NK cells across response states showed distinct enrichment of Pol IIS5P at transcriptional start sites (TSS) versus non-promoter regions with select genes maintaining Pol IIS5P occupancy throughout MCMV infection to the memory phase. Thus, our findings illustrate the dynamic Pol IIS5P genomic occupancy in NK cells during antiviral immunity.
• MEK2 Suppresses IL-4 Polarization via PPARγ and Negatively Impacts Macrophage Epithelial Crosstalk to Delay Repair
  GSE326260Mus musculus12 个样本2026-10-26

  In this study, we tested our hypothesis that MEK2 impairs IL-4 (reparative) macrophage function. Transcriptional profiling of WT and Mek2-/- bone marrow derived macrophages (BMDM) revealed that MEK2 inhibits a subset of IL-4-dependent gene expression, including genes enriched in wound repair pathways.
• 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
• Overlapping MHC class I/II epitopes program monocyte-derived dendritic cells toward a cDC1-like state via mTORC1 pathway inhibition [ChIP-Seq]
  GSE324817Mus musculus12 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-kB-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.
• RNA Polymerase II Dynamics in Antiviral NK Cell Responses [Pol IIS5P CUT&RUN]
  GSE318335Mus musculus22 个样本2026-10-26

  Natural killer (NK) cells are innate lymphocytes that uniquely exhibit both innate and adaptive responses towards certain pathogens. During cytomegalovirus (CMV) infection, antigen-specific NK cells will generate a long-lived pool of memory cells with enhanced responses to secondary infection. The underlying molecular mechanisms that regulate early innate effector functions and delayed adaptive proliferation followed by longevity during antiviral NK cell differentiation remain to be fully understood. Here, we investigated the dynamics of serine-5 phosphorylated RNA Polymerase II (Pol IIS5P) occupancy in NK cells ex vivo during mouse CMV (MCMV) infection. During the initial NK cell antiviral response, Pol IIS5P occupancy increased broadly across the genome, at both upregulated and downregulated genes relative to NK cells at rest. NK cells across response states showed distinct enrichment of Pol IIS5P at transcriptional start sites (TSS) versus non-promoter regions with select genes maintaining Pol IIS5P occupancy throughout MCMV infection to the memory phase. Thus, our findings illustrate the dynamic Pol IIS5P genomic occupancy in NK cells during antiviral immunity.
• Placental insufficiency causes fetal growth restriction in mice lacking Delta-like homologue 1
  GSE313753Mus musculus31 个样本2026-10-26

  Fetal growth restriction (FGR) affects between 3-7% of pregnancies, is associated with increased perinatal morbidity and mortality, and linked to failure of placental function. The placenta is the key transient organ in pregnancy that makes direct contact with the maternal circulation and directs nutrient transfer, intermediary metabolism and the production of hormones that drive maternal metabolic adaptations essential for pregnancy and lactation. The exchange surface of the placenta is formed in early development by the interaction between trophoblast cells that enclose the maternal blood and extraembryonic mesodermal cells that comprise the fetal vasculature. Despite recent insights into trophoblast development derived from novel in-vitro approaches, the processes driving extraembryonic mesoderm development are not well explored. This is due to a dearth of studies employing unbiased approaches to interrogate extraembryonic mesoderm cell populations. Here we use genetic labelling techniques to separate molecular events occurring in the trophoblast from those in the mesodermal layers of the placenta. In combination with conditional targeting, we show that the imprinted gene Dlk1 is a key player in providing nutrients to the embryo by controlling the placental surface area available for nutrient exchange, and by modulating the production of placental hormones that promote maternal nutrient provision in pregnancy.
• A Novel Syngeneic Mouse Model of Metastatic Hormone-Sensitive Prostate Cancer Provides a Platform for Studying Combination Immunotherapy II
  GSE312299Mus musculus2 个样本2026-10-26

  Immunocompetent, hormone-sensitive models of metastatic prostate adenocarcinoma remain limited. We established PL051, a syngeneic luciferase-labeled cell line derived from a Pten^pc-/-;Lkb1^pc-/- (PTEN/LKB1-deficient) mouse background, and profiled its genome and transcriptome alongside tumors from the progenitor GEMM. Whole-exome sequencing (WES) of matched samples shows that PL051 is genetically near-identical to the primary tumor: we detected only one high-confidence somatic coding variant, and copy-number alterations (CNAs) were minimal, with <20% of the captured exome altered. CNAs were predominantly focal (~1–3 kb) and gene-sparse. To map androgen-receptor (AR) signaling at the transcript level, we performed RNA-seq on PL051 following vehicle, dihydrotestosterone (DHT), enzalutamide, and the DHT+enzalutamide combination. The dataset captures agonist-induced AR target activation and antagonist-associated transcriptional shifts (including cell-cycle effects), providing a resource to interrogate AR pathway dynamics in an immune-competent, metastatic context. Together, these data benchmark PL051 as a faithful, transplantable derivative of the GEMM and supply harmonized genomic and transcriptomic profiles suitable for comparative and mechanistic analyses.
• A Novel Syngeneic Mouse Model of Metastatic Hormone-Sensitive Prostate Cancer Provides a Platform for Studying Combination Immunotherapy
  GSE312104Mus musculus16 个样本2026-10-26

  Immunocompetent, hormone-sensitive models of metastatic prostate adenocarcinoma remain limited. We established PL051, a syngeneic luciferase-labeled cell line derived from a Pten^pc-/-;Lkb1^pc-/- (PTEN/LKB1-deficient) mouse background, and profiled its genome and transcriptome alongside tumors from the progenitor GEMM. Whole-exome sequencing (WES) of matched samples shows that PL051 is genetically near-identical to the primary tumor: we detected only one high-confidence somatic coding variant, and copy-number alterations (CNAs) were minimal, with <20% of the captured exome altered. CNAs were predominantly focal (~1–3 kb) and gene-sparse. To map androgen-receptor (AR) signaling at the transcript level, we performed RNA-seq on PL051 following vehicle, dihydrotestosterone (DHT), enzalutamide, and the DHT+enzalutamide combination. The dataset captures agonist-induced AR target activation and antagonist-associated transcriptional shifts (including cell-cycle effects), providing a resource to interrogate AR pathway dynamics in an immune-competent, metastatic context. Together, these data benchmark PL051 as a faithful, transplantable derivative of the GEMM and supply harmonized genomic and transcriptomic profiles suitable for comparative and mechanistic analyses.
• 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