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。

• Exposure to perfluorooctanoic acid perturbs serotonin signaling in maternal pancreatic islets and induces gestational diabetes in mice
  GSE330582Mus musculus8 个样本2026-10-31

  [working abstract for manuscript, in style of how is required for EHP] Background: Perfluorooctanoic acid (PFOA) has been linked to gestational diabetes and other adverse pregnancy outcomes in humans. Despite the association, the mechanisms by which PFOA contributes to GDM have not been studied. The present study investigated whether PFOA exposure resulted in lower pancreatic islet serotonin abundance and β-cell proliferation, glucose intolerance, impaired insulin secretion, insulin resistance, and robust transcriptional changes underlying pancreatic islet adaptation, which provided evidence for a mechanism of PFOA-induced GDM. Objectives: The purpose of this study was to assess whether PFOA exposure impairs pancreatic islet serotonin-driven β-cell proliferation and causes GDM in a C57BL/6J mouse model. Methods: Analysis of pancreatic islet serotonin abundance and β-cell proliferation were measured by immunofluorescence. Metabolic assays, including glucose tolerance test, glucose-stimulated insulin secretion, and insulin tolerance test were used to characterize GDM phenotypes. Bulk RNA sequencing was used to analyze differentially expressed genes and gene set enrichment in pancreatic islets isolated from control and PFOA-exposed mice. Results: PFOA exposure lowered islet serotonin abundance and β-cell proliferation in gestational day (GD) 12.5 pregnant dams. PFOA exposure was associated with glucose intolerance, impaired insulin secretion, and insulin resistance in GD16.5 pregnant dams. β-cell proliferation at GD12.5 and glucose tolerance at GD16.5 was improved in PFOA-exposed dams treated with a serotonin receptor 2B agonist (BW-732C86). RNAseq uncovered four differentially expressed genes and a broad reduction in coordinated transcriptional pathway activity in maternal pancreatic islets of PFOA-exposed GD12.5 dams. Discussion: PFOA-induced glucose intolerance was associated with perturbed pancreatic islet serotonin abundance.

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• 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.

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• Intestinal SAA1 and SAA2 regulate the balance between host inflammatory responses and metabolism
  GSE286869Mus musculus40 个样本2026-10-29

  Since their discovery as acute phase reactants, the SAA proteins have been an important focus of innate immunity research. Most SAA production is in the liver, and despite recent findings of their roles in promoting intestinal immunity, the precise functions of intestinal SAAs have not been well-studied. Validating and using an SAA1/2 double knock-out mouse, we found protective effects of SAA1 and SAA2 mitigating systemic and local inflammatory challenges, along with gene-, sex-, and location-specific responses to gut microbiota perturbations. SAA1 and SAA2 expression supports immunological protection in homeostasis but prioritizes metabolic activities under stress. From this work, we propose a new model in which SAA functions to regulate and integrate the interface between metabolism and host responses to inflammatory insults.

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• Bulk RNA-seq atlas of cytokine-polarized murinebone-marrow-derived macrophages (BMDMs) across inflammatory, regulatory, and reparative stimuli
  GSE315641Mus musculus81 个样本2026-10-28

  Macrophages are highly plastic immune cells that adopt diverse functional states in response to local microenvironmental cues. In tissues, they contribute to host defense, maintain homeostasis, and coordinate responses to perturbations such as infection, injury, and inflammation. This functional diversity arises from their ability to integrate signals from cytokines, growth factors, and stromal interactions, particularly during tissue damage when macrophages transition from inflammatory to regulatory and reparative states. Despite increasing recognition of macrophage heterogeneity, most transcriptomic studies of macrophage polarization focus on a limited set of stimuli, providing an incomplete view of the cytokine-driven programs that shape macrophage behavior during inflammation and repair. Key mediators, including IL-4, IL-13, IL-33, IL-6, IL-10, GM-CSF, and TGF-β, induce distinct yet partially overlapping transcriptional responses that give rise to specialized and hybrid macrophage states. However, a systematic comparative analysis of these cytokine-induced programs remains lacking. To address this gap, we performed bulk RNA-sequencing of murine bone marrow–derived macrophages stimulated in vitro with a comprehensive panel of cytokines representing inflammatory, regulatory, and reparative pathways. This dataset enables direct comparison of cytokine-specific transcriptional programs, delineates classical, alternative, and hybrid activation states, and provides a resource for studying the molecular basis of macrophage plasticity.

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• 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.

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• Macrophage lipid signaling drives glioblastoma invasion and represents a therapeutic vulnerability
  GSE348147Mus musculus16 个样本2026-10-27

  Glioblastoma (GBM) is characterized by diffuse infiltration into the surrounding brain, limiting complete surgical resection, the strongest determinant of patient survival. The mechanisms driving this invasive growth remain incompletely understood. Here, we identify a lipid-mediated paracrine signaling axis through which tumor-associated microglia/macrophages promote glioma invasion. Integrating single-cell transcriptomics, spatial lipidomics, and functional perturbation across mouse models and human GBM samples, we show that invading tumor cells engage and reprogram myeloid cells via CSF1R–PI3K signaling. This induces lipid metabolic reprogramming and secretion of bioactive lipids, including lysophosphatidylcholines (LPCs) and lysophosphatidic acids (LPAs), which promote GBM invasion through distinct downstream pathways. Disruption of this myeloid–GBM axis, reduces lipid secretion and suppresses invasion. Targeting downstream LPA–LPAR or YAP/TAZ signaling further constrains invasion in a context-dependent manner. Together, these findings define a lipid-driven circuit linking the tumor microenvironment to glioma invasion and identify strategies to reduce infiltration and improve surgical resection.

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