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。

• Local chromatin, 3D genome folding and transposon cargo shape Sleeping Beauty transposition
  GSE352692Mus musculus489 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 [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.
• Cooperative interaction of Foxp3 and STAT5 confers regulatory T cell fitness by tuning IL-2-induced gene expression [Myc_RNA]
  GSE352602Mus musculus6 个样本2026-10-31

  The transcription factor Foxp3, with its singular role in the differentiation and function of regulatory T (Treg) cells, is thought to modulate their responses to activatory extracellular cues. However, the underlying mechanisms remain largely unknown. Beyond its requirement for Foxp3 induction during Treg differentiation, STAT5 activation downstream of interleukin-2 (IL-2) signaling is essential for the fitness, activation, and suppressive capacity of mature Treg cells. Here, we demonstrate that IL-2-induced phospho-STAT5 directly binds Foxp3, endowing Foxp3 with a new binding specificity and enabling its recruitment to a distinct set of GAS motif-enriched cis-regulatory elements. Using acute chemogenetic and pharmacological protein degradation strategies, we show that Foxp3 selectively modulates STAT5-dependent transcriptional responses of activated Treg cells to IL-2, including a Myc-dependent gene module. These results suggest that Foxp3-STAT5 complexes “customize” transcriptional responses of activated Treg cells to IL-2 stimulation to support their fitness and functionality.
• 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.
• Local chromatin, 3D genome folding and transposon cargo shape Sleeping Beauty transposition [tagmap]
  GSE352288Mus musculus481 个样本2026-10-31

  The cut-and-paste DNA transposon Sleeping Beauty (SB) is widely used for genome engineering, mutagenesis and gene delivery. When mobilized from a genomic donor position (“launch site”), SB preferentially reintegrates locally (< 2 Mb), but factors governing its transposition from genomic sites remain incompletely understood. Here we analysed local transposition experiments in mouse embryonic stem cells to determine the influence of chromatin context and transposon cargo on SB transposition. Transposons in launch sites with transcriptionally active, accessible chromatin showed lower transposition efficiency. Large cargo and cargo with higher transcriptional activity also result in reduced transposition efficiency. After excision, local reintegration patterns closely resembled 3D contact frequencies of the launch site. This indicates that chromosome folding is a major determinant of the transposition pattern. Surprisingly, we did not detect any effect of the destination chromatin composition on reintegration efficiency. Cargo sequence modified the reintegration patterns: promoter-containing cargo increased both very proximal (<10kb) and interchromosomal transpositions, while CTCF binding sites in the cargo increased reintegration on the launch chromosome. Together, these results define key determinants of SB transposition in chromosomes and inform the design of SB-based genome engineering strategies.
• Local chromatin, 3D genome folding and transposon cargo shape Sleeping Beauty transposition [pADam]
  GSE352286Mus musculus8 个样本2026-10-31

  The cut-and-paste DNA transposon Sleeping Beauty (SB) is widely used for genome engineering, mutagenesis and gene delivery. When mobilized from a genomic donor position (“launch site”), SB preferentially reintegrates locally (< 2 Mb), but factors governing its transposition from genomic sites remain incompletely understood. Here we analysed local transposition experiments in mouse embryonic stem cells to determine the influence of chromatin context and transposon cargo on SB transposition. Transposons in launch sites with transcriptionally active, accessible chromatin showed lower transposition efficiency. Large cargo and cargo with higher transcriptional activity also result in reduced transposition efficiency. After excision, local reintegration patterns closely resembled 3D contact frequencies of the launch site. This indicates that chromosome folding is a major determinant of the transposition pattern. Surprisingly, we did not detect any effect of the destination chromatin composition on reintegration efficiency. Cargo sequence modified the reintegration patterns: promoter-containing cargo increased both very proximal (<10kb) and interchromosomal transpositions, while CTCF binding sites in the cargo increased reintegration on the launch chromosome. Together, these results define key determinants of SB transposition in chromosomes and inform the design of SB-based genome engineering strategies.
• Liver Kinase B1 depletion disrupts the pantothenic acid: coenzyme A pathway in astrocytes
  GSE351587Mus musculus8 个样本2026-10-31

  Previous studies showed conditional knockout of Liver Kinase B1 (LKB1) from astrocytes exacerbated disease severity and glial cell activation in a mouse model of Multiple Sclerosis (MS). A major function of LKB1 is to maintain energy supplies under conditions of metabolic stress, suggesting that loss of LKB1 could alter astrocytic metabolic processes. Following siRNA mediated knockdown (KD) of LKB1 from primary mouse astrocytes, untargeted metabolomic screening identified significant increases in Pantothenic Acid (PA) and related metabolites; and pathway analysis showed the PA:Coenzyme A (PA:CoA) pathway was significantly modified. This pathway was also identified by bulk RNA sequencing. In LKB1 KD cells, relative mRNA levels of enzymes in the PA:CoA pathway were reduced, and PA Kinase 2 (Pank2, which converts PA to phosphoPA) expression was reduced. Deficiencies in Pank2 are known to cause iron accumulation, which we confirmed occurs in LKB1 KD astrocytes. The KD cells also showed increased sensitivity to induction of ferroptosis. Measurement of serum PA levels showed a positive correlation with age at diagnosis in relapsing remitting MS patients harboring a variant in the gene encoding LKB1. Together, these results indicate that metabolic disturbance leads to dysregulation of the PA:CoA pathway in astrocytes and suggest that plasma PA levels could provide a novel biomarker for MS disease.
• 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
• Gene Expression in the Glioblastoma Cell Line (GL261) Transcriptome Following Treatment with Magnetic Nanoparticles (MNPQ)
  GSE349688Mus musculus9 个样本2026-10-31

  GL261 cells are a widely used glioma tumor model system; following in situ transplantation, they stably form glioblastoma and are extensively utilized as a preclinical evaluation model for brain gliomas. Magnetic nanomedicines (MNPQ), with their advantages of magnetically responsive targeted enrichment and locally controlled release, have demonstrated effective antitumor potential against gliomas; however, how they reshape the gene expression profile of tumor cells at the transcriptomic level remains unclear. Our study has one primary objective: to identify differentially expressed genes and their enriched signaling pathways in the GL261 cell transcriptome before and after MNPQ treatment, thereby elucidating the molecular mechanisms underlying its antitumor effects.
• 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.
• Gene expression in pericental and periportal hepatocytes
  GSE349461Mus musculus4 个样本2026-10-31

  Hepatic metabolic zonation enables periportal (PP) and pericentral (PC) hepatocytes to perform distinct metabolic functions. To characterize spatial differences in hepatic gene expression, we isolated PP and PC hepatocytes from mouse liver and performed RNA sequencing. This dataset provides transcriptomic profiles of PP and PC hepatocytes and enables identification of genes and pathways differentially regulated across the portal-to-central vein axis.

  空间转录组
• 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.
• Id2 orchestrates IL-33-driven metabolic reprogramming in pathogenic Th2 cells (RNA-seq)
  GSE344612Mus musculus8 个样本2026-10-31

  The transcription factor Id2 licenses the transition of stem‑like Th2 cells to pathogenic ST2⁺ Tpath2 cells by orchestrating IL‑33‑ST2 signaling to drive glycolytic reprogramming. Id2 transcriptionally represses Pten by sequestering E proteins at its promoter, amplifying PI3K‑AKT signaling and glycolytic flux, which supports histone acetylation at Il1rl1 and Il5. Id2‑deficient Th2 cells fail to establish this epigenetic state; pyruvate supplementation rescues the defect. Pharmacological Id2 inhibition attenuates Tpath2 responses and airway inflammation in vivo, and cross‑species analysis confirms conserved PTEN dynamics in human asthma. Thus, the IL‑33–Id2–PI3K‑AKT axis represents a metabolic–epigenetic checkpoint and therapeutic target for allergic airway disease.
• 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.
• Local effect of Ixodes scapularia TNFBP gene silence on transcriptome of bitten skin of mouse
  GSE344220Mus musculus9 个样本2026-10-31

  To explore their potential role in tick-host interactions, RNA-seq was performed on the skin of mice bitten by TNFBP1 and TNFBP2 silenced ticks. The transcriptome was altered after feeding on gene silenced ticks compared with control ticks, and defined pathways including legionellosis, HIF-1TNF, IL-17 signaling pathway, phagosome were significantly enriched in the downregulated genes.
• Specification of bone marrow sinusoids requires TIE2-mediated positive feedback involving COUP-TFII and VEGFR3 [Nr2f2_ecko P5bm]
  GSE342123Mus musculus6 个样本2026-10-31

  The bone marrow (BM) vascular network drives bone development and supports hematopoiesis, yet the mechanisms governing its specialized sinusoidal architecture remain poorly characterized. Here, we show that the angiopoietin receptor TIE2 is highly expressed by BM sinusoidal endothelial cells (BM_SECs), and its endothelial deletion triggers sinusoidal capillarization, characterized by reduced vessel diameter and aberrant mural cell coverage. Mechanistically, TIE2 insufficiency drives a downregulation of VEGFR3 in BM_SECs, while leaving hepatic sinusoidal VEGFR3 unaffected. Notably, BM sinusoidal VEGFR3 downregulation occurred within 48 hours of induced endothelial Tek deletion. RNA-sequencing revealed that TIE2 insufficiency downregulated pathways related to sinusoidal development, alongside an aberrant upregulation of arterial and angiogenic genes. We validated this phenotype using inducible Tek deletion specifically within VEGFR3+ SECs, or in mutant mice with the insufficiency of TIE2 ligand ANGPT1. Furthermore, endothelial deletion of the transcription factor Nr2f2 (COUP-TFII) recapitulated these defects, yielding reductions in BM sinusoidal TIE2 and VEGFR3 expression. Finally, induced endothelial deletion of Flt4 produced a similar phenotype of defective BM sinusoidal formation. Together, our findings demonstrate that ANGPT1/TIE2 and COUP-TFII form a reciprocal regulatory loop essential for coordinating BM sinusoidal specification by sustaining VEGFR3 expression.
• Specification of bone marrow sinusoids requires TIE2-mediated positive feedback involving COUP-TFII and VEGFR3 [Tek_ecko P3bm]
  GSE342122Mus musculus8 个样本2026-10-31

  The bone marrow (BM) vascular network drives bone development and supports hematopoiesis, yet the mechanisms governing its specialized sinusoidal architecture remain poorly characterized. Here, we show that the angiopoietin receptor TIE2 is highly expressed by BM sinusoidal endothelial cells (BM_SECs), and its endothelial deletion triggers sinusoidal capillarization, characterized by reduced vessel diameter and aberrant mural cell coverage. Mechanistically, TIE2 insufficiency drives a downregulation of VEGFR3 in BM_SECs, while leaving hepatic sinusoidal VEGFR3 unaffected. Notably, BM sinusoidal VEGFR3 downregulation occurred within 48 hours of induced endothelial Tek deletion. RNA-sequencing revealed that TIE2 insufficiency downregulated pathways related to sinusoidal development, alongside an aberrant upregulation of arterial and angiogenic genes. We validated this phenotype using inducible Tek deletion specifically within VEGFR3+ SECs, or in mutant mice with the insufficiency of TIE2 ligand ANGPT1. Furthermore, endothelial deletion of the transcription factor Nr2f2 (COUP-TFII) recapitulated these defects, yielding reductions in BM sinusoidal TIE2 and VEGFR3 expression. Finally, induced endothelial deletion of Flt4 produced a similar phenotype of defective BM sinusoidal formation. Together, our findings demonstrate that ANGPT1/TIE2 and COUP-TFII form a reciprocal regulatory loop essential for coordinating BM sinusoidal specification by sustaining VEGFR3 expression.
• Specification of bone marrow sinusoids requires TIE2-mediated positive feedback involving COUP-TFII and VEGFR3 [Tek_ecko P11bm]
  GSE342121Mus musculus6 个样本2026-10-31

  The bone marrow (BM) vascular network drives bone development and supports hematopoiesis, yet the mechanisms governing its specialized sinusoidal architecture remain poorly characterized. Here, we show that the angiopoietin receptor TIE2 is highly expressed by BM sinusoidal endothelial cells (BM_SECs), and its endothelial deletion triggers sinusoidal capillarization, characterized by reduced vessel diameter and aberrant mural cell coverage. Mechanistically, TIE2 insufficiency drives a downregulation of VEGFR3 in BM_SECs, while leaving hepatic sinusoidal VEGFR3 unaffected. Notably, BM sinusoidal VEGFR3 downregulation occurred within 48 hours of induced endothelial Tek deletion. RNA-sequencing revealed that TIE2 insufficiency downregulated pathways related to sinusoidal development, alongside an aberrant upregulation of arterial and angiogenic genes. We validated this phenotype using inducible Tek deletion specifically within VEGFR3+ SECs, or in mutant mice with the insufficiency of TIE2 ligand ANGPT1. Furthermore, endothelial deletion of the transcription factor Nr2f2 (COUP-TFII) recapitulated these defects, yielding reductions in BM sinusoidal TIE2 and VEGFR3 expression. Finally, induced endothelial deletion of Flt4 produced a similar phenotype of defective BM sinusoidal formation. Together, our findings demonstrate that ANGPT1/TIE2 and COUP-TFII form a reciprocal regulatory loop essential for coordinating BM sinusoidal specification by sustaining VEGFR3 expression.
• 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