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。

• Cooperative interaction of Foxp3 and STAT5 confers regulatory T cell fitness by tuning IL-2-induced gene expression [ATAC-Seq]
  GSE352613Mus musculus32 个样本2026-10-31

  Transcription factor Foxp3, with its singular role in differentiation and function of regulatory T (Treg) cells in physiologic and inflammatory settings, is thought to act by modulating transcriptional responses to activatory extracellular cues including pro-inflammatory cytokines. However, the underlying mechanisms remain largely unknown. After Foxp3 is induced during Treg differentiation upon STAT5 activation downstream of interleukin-2 receptor (IL-2R), sustained STAT5 signaling facilitates fitness and suppressive capacity of mature Treg cells. We found that Foxp3 and phospho-STAT5 (pSTAT5) form a stable transcriptional complex. Upon IL-2 sensing, Foxp3 is recruited in a pSTAT5-dependent manner to GAS-motif-enriched cis-regulatory elements that are developmentally primed by STAT5 in Treg precursors prior to Foxp3 expression. Using chemogenetically and pharmacologically induced protein degradation, we demonstrate that Foxp3 modulates STAT5 signaling in activated Treg cells to selectively modulate their transcriptional response to IL-2, most prominently involving a Myc-dependent gene module. Our studies suggest that direct Foxp3-STAT5 cooperativity fine-tunes STAT5 signaling downstream of IL-2 receptor activation to support functionality of differentiated Treg cells.
• Gut microbial equol production associates with cognitive trajectories and suppresses NLRP3 inflammasome activation
  GSE352509Mus musculus12 个样本2026-10-31

  Many intestinal microbiome-produced metabolites have neuroimmunomodulatory properties. To identify metabolites associated with cognition and neuroinflammation, we measured microbially derived metabolites in the blood serum of 1,206 cognitively normal participants from the Wisconsin Alzheimer’s Disease Research Center (ADRC) and the Wisconsin Registry for Alzheimer’s Prevention (WRAP). We found that serum presence of equol, a microbially-produced metabolite derived from the soy-isoflavone daidzein, was related to preclinical cognition over time in a sex-dependent manner, suggesting that microbe-derived equol may attenuate cognitive decline through sex-specific biological pathways. Additionally, serum equol was associated with slower accumulation of the CSF biomarkers GFAP, S100B, and NfL, suggesting equol may be linked to glial regulation and neuronal integrity. To understand how equol may mediate inflammation systemically to reduce neuroinflammation, we performed bulk RNA-sequencing on bone marrow-derived macrophages (BMDMs) and found S-equol treatment modestly altered pathways associated with the NOD, LRR, and pyrin domain containing (NLRP3) inflammasome, an established driver of neuroinflammation in Alzheimer’s disease. We used ELISAs and caspase-1 immunoblots to show S-equol inhibits NLRP3 activation in BMDMs, evidenced by significantly decreased IL-1β secretion and caspase-1 processing after equol treatment. We confirmed that this effect is directly dependent on equol’s inhibition of potassium efflux. These findings lay a strong foundation for future studies examining the neuroimmunomodulatory action of equol in NLRP3 driven disease and cognitive decline.
• Targeting the Alk4 pathway protects against age-related bone loss.
  GSE352343Mus musculus15 个样本2026-10-31

  Osteoporosis is a chronic age-related condition where imbalanced activities between bone-forming osteoblasts and bone-resorbing osteoclasts result in the progressive loss of bone volume and reduced bone quality. While drugs that target osteoclast activity have been developed, there remains a lack of efficient therapies that increase osteoblast function in aging bones. Here, we showed that in mouse femurs, levels of Activin signaling progressively increased with age and strongly correlated with the loss of trabecular bone. When we removed Alk4, the type I receptor for Activin in osteoblast progenitors, Alk4 cKO mice had increased numbers of osteoblasts, an increased rate of bone formation, and increased trabecular bone acquisition. These results indicate that Activin through Alk4 signaling inhibits bone formation and osteoblast activity and is likely associated with osteoporosis. Furthermore, when we injected 2-year-old male mice with Alk4-Fc to capture circulating Activin, aged mice were protected against loss of trabecular bone in both femurs and L5 vertebrae. Remarkably, Alk4-Fc also prevented the age-related decrease in muscle mass that normally accompanies age-related bone loss, indicating that circulating Activins also play a role in sarcopenia. In summary, our preclinical mouse models reveal that circulating Activins play a primary role in age-related bone and muscle loss and can be efficiently targeted to alleviate osteoporosis and sarcopenia in aging mice.
• RNA-seq of mouse bone marrow mesenchymal stem cells treated with different NPY concentrations
  GSE349627Mus musculus12 个样本2026-10-31

  Mouse bone marrow mesenchymal stem cells (BMSCs) were treated with neuropeptide Y (NPY) at 0, 1e-8, 1e-7, or 1e-6 mM for 7 or 14 days. Twenty-four polyA UID-mRNA-seq paired-end libraries (three biological replicates per treatment and time point) were sequenced to assess transcriptomic changes associated with low versus high NPY intervention.
• 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
• Sleep-dependent DNA methylation remodeling in basolateral amygdala fear engrams
  GSE348542Mus 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. Here, we performed whole-genome bisulfite sequencing (WGBS) on fear conditioning (FC)-activated cells from the BLAs of adult male mice experiencing sleep or sleep deprivation following FC learning, at a week (day 7) and a month (day 28) timepoints. This dataset enables the investigation of cytosine methylation changes (CG and non-CG contexts) associated with learning-induced epigenomic programming in the BLA.
• Sleep-dependent DNA methylation remodeling in basolateral amygdala fear engrams [batch 1 WGBS]
  GSE348488Mus musculus12 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. Here, we performed whole-genome bisulfite sequencing (WGBS) on fear conditioning (FC)-activated cells from the BLAs of adult male mice experiencing sleep or sleep deprivation following FC learning, at a week (day 7) and a month (day 28) timepoints. This dataset enables the investigation of cytosine methylation changes (CG and non-CG contexts) associated with learning-induced epigenomic programming in the BLA.
• Sleep-dependent DNA methylation remodeling in basolateral amygdala fear engrams [batch 2 WGBS]
  GSE348480Mus 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. Here, we performed whole-genome bisulfite sequencing (WGBS) on fear conditioning (FC)-activated cells from the BLAs of adult male mice experiencing sleep or sleep deprivation following FC learning, at a week (day 7) and a month (day 28) timepoints. This dataset enables the investigation of cytosine methylation changes (CG and non-CG contexts) associated with learning-induced epigenomic programming in the BLA.
• Functional landscape of enhancers that control the blood-brain barrier
  GSE347657Mus musculus21 个样本2026-10-31

  Cis-regulatory elements (CREs) that control of the blood-brain barrier (BBB) transcriptional program have been studied by transducing candidate CREs together with a GFP reporter into mouse brain endothelial cells (ECs) in vivo using recombinant Adeno-Associated Viruses (rAAVs). Approximately one-quarter of DNA segments encompassing regions of accessible chromatin (ATACseq peaks) in or near 16 genes that are highly expressed in CNS ECs confer brain EC gene expression when transduced using rAAVs. For six active CREs, site-directed mutagenesis showed that ERG/ETS and LEF/TCF motifs are consistently important for CRE activity, while FOX and ZIC motifs are variably important for CRE activity. Transcription factor (TF) occupancy maps, determined by the CUT&RUN method for ERG, LEF1, KLF4, and ZIC3 in and near the same 16 genes in acutely isolated mouse brain ECs, showed that one or more of these TFs occupied binding sites in nearly all of the 55 candidate CREs, with a modestly higher occupancy level among the 14 candidate CREs that were active in vivo in the rAAV assay compared to the 41 candidate CREs that were inactive in vivo in the rAAV assay. As observed previously for ERG and LEF1 (Li et al., 2026), chromatin occupancy by KLF4 and ZIC3 is highly enriched in open chromatin that is brain EC-specific, regions that represent the strongest candidates for brain EC-specific CREs. These studies provide foundational information for research aimed at generating endothelial cells with BBB properties in vitro.
• Pericytes modulate brain vascular integrity in social stress in mice and human depression
  GSE347183Mus musculus10 个样本2026-10-31

  Major depressive disorder (MDD) is a leading cause of disease burden with low therapeutic efficacy. Chronic social stress, MDD’s main risk factor, is associated with neurovascular pathology in mood-regulating brain regions. Pericytes ensheathe endothelial cells and modulate blood-brain barrier (BBB) functions, but contribution of these mural cells to stress responses or psychiatric conditions is unknown. Here, we show sex-specific transcriptomic, morphological and functional alterations in pericytes in the prefrontal cortex (PFC) following stress exposure in female mice and women with MDD. Endothelial cell-to-pericyte crosstalk via PDGFB:PDGFRB signaling is important for BBB dynamics. Reduction of Pdgfrb+ pericyte coverage in the PFC induces anxiety- and depression-like behaviours in female, but not male mice, while viral-mediated increased pericyte-endothelial communication promotes stress coping. RNA-seq of human endothelial cells and pericytes exposed to MDD serum reveals changes in extracellular matrix-related genes and cell-cell communication. PDGF-BB serum level correlates with depressive symptoms and diagnosis. Altogether, our findings shed light on a mechanism underlying PFC dysfunction in MDD, a therapeutic target and blood biomarker. Our work provides tools to manipulate pericytes applicable for vascular, neurodegenerative, or inflammatory diseases all characterized by high rates of depression.
• GR signaling impairs osteoblast differentiation via Map7d2
  GSE346858Mus musculus14 个样本2026-10-31

  The glucocorticoid receptor (GR) is an important regulator of skeletal homeostasis; however, the molecular mechanisms through which it regulates osteogenic differentiation remain incompletely understood. Here, we investigated the role of GR using two complementary primary murine osteogenic cell models, bone marrow stromal cells (BMSCs) and bone-derived primary osteoblasts (pOs), together with comparative transcriptomic analyses. RNA sequencing (RNAseq) revealed extensive transcriptional changes following GR knockdown. Despite substantial differences in gene expression profiles of the two osteogenic cell models, pathway enrichment analyses revealed common biological processes, including MAPK signaling and cell migration. Comparative transcriptomic analysis further identified only 17 genes that were consistently regulated in the same direction in both cell preparations, among which Map7d2 emerged as a previously unrecognized GR-responsive candidate. Co-depletion of Map7d2 partially rescued the impairment of osteogenic differentiation caused by GR depletion.Taken together, our study reveals common molecular responses to GR depletion across two primary murine osteogenic cell models and provides new insights into the transcriptional and signaling networks underlying GR-regulated osteogenic differentiation.
• Tissue Nano-Transfection Promotes Vascularization to Enhance Acellular Nerve Allograft–Mediated Nerve Repair
  GSE344504Mus musculus16 个样本2026-10-31

  Peripheral nerves possess an inherent capacity for regeneration, yet functional recovery following an injury remains inconsistent despite advances in microsurgical repair. Autologous nerve grafts are the gold standard for complex peripheral nerve injuries (PNI) but are constrained by limited donor availability, donor-site morbidity, and size mismatches. Acellular nerve allografts (ANAs) offer off-the-shelf availability and can bridge longer defects, but their performance is hindered by the lack of intrinsic Schwann cells and vascular structures, essential for axonal regeneration. Here, we report on the use of Tissue Nanotransfection (TNT), a novel non-viral platform that allows the delivery of nucleic acids into solid tissues in combination with ANAs. We used TNT to reprogram resident nerve cells toward a vasculogenic phenotype to locally increase vascularization and improve outcomes following PNI reconstruction. We show that vasculogenic transcription factors (Etv2, Fli1, and Foxc2; EFF) drive transcriptomic changes in vitro. In vivo, vasculogenic TNT increases the number of endothelial cells within ANAs as early as 5 weeks post-treatment. Mice receiving ANAs combined with vasculogenic TNT exhibited superior functional recovery, including enhanced muscle strength and progressive restoration outperforming ANAs only controls. Region-specific transcriptomics reveal that the site of the TNT application along the host nerve critically influences the regenerative response. Together, these findings identify vasculogenic TNT as a potent, non-viral strategy to enhance ANA-mediated repair by promoting localized vasculogenesis and supporting improved functional recovery and muscle protection.
• Paternal methylphenidate exposure alters sperm miRNAs and induces intergenerational behavioral and transcriptional changes that are largely reversed by washout
  GSE341541Mus musculus12 个样本2026-10-31

  To determine whether paternal methylphenidate exposure alters sperm small noncoding RNA profiles and whether these changes are reversible after drug withdrawal, male BALB/c mice were administered methylphenidate (15 mg/kg) or saline (10 mL/kg) for 28 days. Cauda epididymal sperm were collected immediately after treatment or after a 40-day washout period and analyzed by small RNA sequencing.
• Targeting ERO1α Triggers Tumor Immunosurveillance in Triple-Negative Breast Cancer
  GSE337796Mus musculus24 个样本2026-10-31

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Targeting ERO1α Triggers Tumor Immunosurveillance in Triple-Negative Breast Cancer [RNA-seq]
  GSE337795Mus 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.
• 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
• MORC2A is required for DNA methylation and H3K9me3 at retrotransposons in the male germline
  GSE335170Mus musculus29 个样本2026-10-31

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• MORC2A is required for DNA methylation and H3K9me3 at retrotransposons in the male germline [RNA-seq]
  GSE335166Mus musculus10 个样本2026-10-31

  Transposable elements pose a particular threat to the germline, where their activation can compromise fertility and generate heritable mutations. In male germ cells, transposon silencing depends on repressive epigenetic states, including CpG methylation and H3K9me3. Here, we identify MORC2A as an essential regulator of transposon repression in the mouse male germline. Conditional deletion of Morc2a in primordial germ cells caused complete male infertility, testicular atrophy, germ cell loss and meiotic arrest. MORC2A-deficient testes displayed derepression of evolutionarily young retrotransposons, accompanied by DNA damage and apoptosis. Genome-wide profiling revealed loss of CpG methylation and H3K9me3 at these elements. Small RNA sequencing showed that piRNA biogenesis and ping-pong amplification remain largely intact. Together, these datasets identify MORC2A as a male germline chromatin regulator required for epigenetic silencing of young transposable elements.
• 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
• GPR124 upregulation protects AML blasts from lipotoxicity
  GSE329506Mus musculus12 个样本2026-10-31

  GPR124 (ADGRA2), a member of the Adhesion G Protein-Coupled Receptor family, has an established role in the embryonic development of the central nervous system vasculature. However, its function in the context of acute myeloid leukemia (AML) remains unexplored. Transcriptome studies revealed upregulation of GPR124 in AML CD34+ blasts compared to healthy counterparts. Lentiviral overexpression of an GPR124-EGFP fusion protein indicated both plasma membrane and intracellular localization. Immunoprecipitation followed by LC-MS/MS showed strong enrichment of intracellular proteins associated with vesicles and vesicle transport, focal adhesion, actin cytoskeleton, and lipid droplets (LDs). In murine bone marrow mesenchymal stromal cells stimulated towards adipocytic differentiation, CRISPR-Cas9 mediated knockout of Gpr124 (Gpr124KO) reduced LD size, while total neutral lipid accumulation showed an increasing trend. In AML cells, lipidomic studies revealed increased baseline triacylglycerol (TG) levels in GPR124KO cells, suggesting altered LD metabolism. Since TGs are key components of LDs and its accumulation is a known response to lipid peroxidation, we next assessed ferroptosis sensitivity. Indeed, GPR124KO cells were significantly more sensitive to ferroptosis induction by GPX4 inhibition, accompanied by increased reactive oxygen species (ROS) and accumulation of lipid peroxidation. Additionally, GPR124KO cells were more sensitive to DGAT1 inhibition, a key enzyme in LD formation, and combination with the ferroptosis inducer RSL3 was synergistic in GPR124KO cells. Together, our findings indicate that GPR124 is essential for maintaining stable lipid homeostasis in AML and identify GPR124 and LD metabolism as potential therapeutic targets for inducing ferroptosis-mediated cell death.
• Small RNA sequencing of fibrotic intestinal tissues from TNBS-induced mice
  GSE326149Mus musculus10 个样本2026-10-31

  To investigate miRNA expression changes associated with intestinal fibrosis, we performed small RNA sequencing on colon tissues from TNBS-induced fibrotic mice and control mice. This dataset was generated to identify fibrosis-associated miRNAs and provide a basis for subsequent functional and mechanistic studies of intestinal fibrosis.
• mRNA expression profiling of intestinal fibrosis in TNBS-induced mice
  GSE326147Mus musculus10 个样本2026-10-31

  To characterize transcriptomic alterations associated with intestinal fibrosis, we performed mRNA sequencing on colon tissues from TNBS-induced fibrotic mice and control mice. This dataset was generated to identify differentially expressed genes and signaling pathways involved in intestinal fibrosis.
• RNA-seq of Mus musculus 2-cell embryos (WT vs Tcl1 KO) with CDCA treatment
  GSE323388Mus musculus14 个样本2026-10-31

  This study includes paired-end bulk RNA-seq data generated from Mus musculus embryos at the 2-cell stage. Samples comprise wild-type (WT) and Tcl1 knockout (KO) embryos, with and without CDCA treatment, with biological replicates. Raw sequencing data are available in SRA and linked here via SRA Run accessions.
• Cooperative interaction of Foxp3 and STAT5 confers regulatory T cell fitness by tuning IL-2 induced gene expression
  GSE311192Mus musculus27 个样本2026-10-31

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Cooperative interaction of Foxp3 and STAT5 confers regulatory T cell fitness by tuning IL-2 induced gene expression [Cut & Run]
  GSE311187Mus musculus15 个样本2026-10-31

  Transcription factor Foxp3, with its singular role in differentiation and function of regulatory T (Treg) cells in physiologic and inflammatory settings, is thought to act by modulating transcriptional responses to activatory extracellular cues including pro-inflammatory cytokines. However, the underlying mechanisms remain largely unknown. After Foxp3 is induced during Treg differentiation upon STAT5 activation downstream of interleukin-2 receptor (IL-2R), sustained STAT5 signaling facilitates fitness and suppressive capacity of mature Treg cells. We found that Foxp3 and phospho-STAT5 (pSTAT5) form a stable transcriptional complex. Upon IL-2 sensing, Foxp3 is recruited in a pSTAT5-dependent manner to GAS-motif-enriched cis-regulatory elements that are developmentally primed by STAT5 in Treg precursors prior to Foxp3 expression. Using chemogenetically and pharmacologically induced protein degradation, we demonstrate that Foxp3 modulates STAT5 signaling in activated Treg cells to selectively modulate their transcriptional response to IL-2, most prominently involving a Myc-dependent gene module. Our studies suggest that direct Foxp3-STAT5 cooperativity fine-tunes STAT5 signaling downstream of IL-2 receptor activation to support functionality of differentiated Treg cells.
• Cooperative interaction of Foxp3 and STAT5 confers regulatory T cell fitness by tuning IL-2 induced gene expression [RNA-Seq]
  GSE311182Mus musculus12 个样本2026-10-31

  Transcription factor Foxp3, with its singular role in differentiation and function of regulatory T (Treg) cells in physiologic and inflammatory settings, is thought to act by modulating transcriptional responses to activatory extracellular cues including pro-inflammatory cytokines. However, the underlying mechanisms remain largely unknown. After Foxp3 is induced during Treg differentiation upon STAT5 activation downstream of interleukin-2 receptor (IL-2R), sustained STAT5 signaling facilitates fitness and suppressive capacity of mature Treg cells. We found that Foxp3 and phospho-STAT5 (pSTAT5) form a stable transcriptional complex. Upon IL-2 sensing, Foxp3 is recruited in a pSTAT5-dependent manner to GAS-motif-enriched cis-regulatory elements that are developmentally primed by STAT5 in Treg precursors prior to Foxp3 expression. Using chemogenetically and pharmacologically induced protein degradation, we demonstrate that Foxp3 modulates STAT5 signaling in activated Treg cells to selectively modulate their transcriptional response to IL-2, most prominently involving a Myc-dependent gene module. Our studies suggest that direct Foxp3-STAT5 cooperativity fine-tunes STAT5 signaling downstream of IL-2 receptor activation to support functionality of differentiated Treg cells.
• Social Stress Differentially Affects the Behavior and the Transcriptome of the adBNST between Male and Female Mice.
  GSE287634Mus musculus20 个样本2026-10-31

  Stress can be broken down into systemic and processive stressors with processive stressors requiring higher limbic processing. These are also often called social stressors as they require an understanding of social dynamics as opposed to physical based stressors. This differing of processing necessitates we study both phenomena. Additionally, sex is an important aspect of stress research as men and women show differing responses to stress and mood disorder development. To study this, we used a chronic social instability stress (CSIS) paradigm to stress male and female mice. This paradigm is approximately 7-weeks long and involves changing the cage mates of a mouse every 3 days so stable social dynamics cannot form. Afterwards, one cohort was used for avoidance behavior testing using the open field test, the elevated plus maze, the light/dark box emergence test, and the novelty suppressed feeding test. A second cohort was used for bulk RNA-Sequencing of the anterodorsal bed nucleus of the stria terminalis which is a limbic structure known to be related to chronic stress signaling. In the behavior assays, CSIS caused the females to be less avoidant, while the males became more avoidant. Additionally, we found that a low estrogen state in the females caused them to be less avoidant than in a high estrogen state. In the transcriptome, we found major differences between the males and females with the males expressing more genes related to transcription whereas the females expressed more genes related to synaptic transmission. We also found that the transcriptome in the males is more sensitive to the stress than the females. In summary, we have found how social stress is differentially regulated between males and females and how this may be related to the development of stress-related behavioral changes.
• Nephrin-associated phospho-protein network necessary for filtration at the slit-diaphragm and podocyte adhesion.
  GSE284774Mus musculus25 个样本2026-10-31

  Minimal Change Disease (MCD) is characterized by nephrotic syndrome. In a subgroup of patients, pathogenic antibodies against the slit-diaphragm (SD) protein Nephrin encoded by the gene NPSH1 were identified in blood and biopsy samples. Nephrin is essential for the SD as specific NPHS1 variants result in congenital nephrotic syndrome. Intact Nephrin is a structural component of the SD, but also transmits signals to the actin cytoskeleton of podocyte foot processes (FP) thereby presumably stabilizing podocyte FP morphology. Thus, analyzing the Nephrin signalosome is attractive to identify potential targets for therapeutic intervention in MCD. We employed a model of MCD with antibody-mediated clustering of Nephrin leading to tyrosine phosphorylation-dependent signal transduction in podocyte culture. Phospho-proteome analysis after antibody-mediated Nephrin clustering revealed approx. 180 differentially phosphorylated peptides. Gene set analysis showed that among others the biological process ‘cell matrix adhesion’ was enriched. We verified that two thirds of the identified proteins were necessary for filtration in vivo employing a knockdown approach with consecutive analysis by an in-vivo filtration assay in Drosophila melanogaster nephrocytes. One of the phosphorylated proteins following Nephrin activation in the phospho-proteome analysis was the activating factor of the small GTPase Rap1 – Rapgef1. The significance of this Nephrin effector Rapgef1 for SD and focal adhesion integrity was exemplary studied generating a Rapgef1 knockout (Rapgef1KO) in the metanephric mesenchyme of mice. We confirmed that an early Rapgef1 knockout in podocytes - like transgenic Nephrin mice deficient in tyrosine-dependent signaling – resulted in nephrotic syndrome and an MCD/focal segmental glomerulosclerosis (FSGS) phenotype. RNA sequencing of Rapgef1 knockout mice glomeruli revealed significant regulation of genes involved in cell signaling, cell adhesion, and extracellular matrix organization. Changes in glomerular basement membrane (GBM), focal adhesion (FA) composition, and significant podocyte loss were confirmed by immunofluorescence analysis in Rapgef1 knockout mice glomeruli. Altogether, we identified a Nephrin-associated phospho-protein network necessary for filtration at the slit-diaphragm and podocyte adhesion.
• Krüppel-like factor 5 remodels lipid metabolism in exercised skeletal muscle
  GSE279425Mus musculus16 个样本2026-10-31

  Regular physical activity induces a variety of health benefits, preventing and counteracting diseases caused by a sedentary lifestyle. However, the molecular underpinnings of skeletal muscle plasticity in exercise remain poorly understood. We identified a role of the Krüppel-Like Factor 5 (Klf5) in this process, in particular in the regulation of lipid homeostasis. Surprisingly, gain- and loss-of-function studies in muscle in vivo revealed seemingly opposite functions of Klf5 in the response to an acute exercise bout and chronic training, modulating lipid oxidation and synthesis, respectively. Thus, even though only transiently induced, the function of Klf5 is complex and integral for a normal long-term training response. These findings highlight the importance of this mediator of external stress response to adaptive remodeling of skeletal muscle tissue.