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。

• The metabolic reprogramming of T cells controls airway remodeling in severe asthma
  GSE352552Mus musculus10 个样本2026-10-30

  Background: Mixed granulocytic asthma (MGA) is a severe Th2-low endotype, characterized by high Th17/neutrophilic burden and exacerbated airway remodeling. Both features confer resistance to inhaled corticosteroids and typical asthma treatments. Objective: We aimed to address gaps in knowledge, including how Th17 cells induce pathological tissue remodeling and how Th17 differentiation occurs in response to allergens. Methods: We generated a Th2-low murine model of asthma on the Il4rα-/- background that mimics the decrease in type 2 response seen in corticosteroid-resistant patients. We monitored major features of human disease including heightened airway reactivity to methacholine, Th17/neutrophilic inflammation, airway remodeling, and resistance to corticosteroid treatment. Comparative transfer of Th2 versus Th17 cells were analyzed. We further investigated how the mitochondrial oxidative phosphorylation (OXPHOS) pathway modulates pathogenic Th17 cell reprogramming by in vitro T cell cultures and in vivo therapeutic blockades. Results: LIGHT (aka TNFSF14) and the OXPHOS pathway are enriched in human MGA and likewise upregulated in this mouse model. We show OXPHOS promotes the metabolic reprograming of Th17 cells, to sustain their survival despite steroid treatment and produce LIGHT that controls airway remodeling. Mechanistically, OXPHOS regulates RORγt expression and the subsequent transcriptional network to program differentiation of Th17 cells, whereas LIGHT drives airway remodeling by activating the MMP9-dependent TGFβ pathway. Additionally, OXPHOS+Th17 cells promote the expression of osteopontin necessary for fibroblast activation. LIGHT antagonistic blockade reduces airway remodeling, whereas OXPHOS inhibition kills Th17 cells and subsequent neutrophilia. Importantly, the dual blockade of LIGHT and OXPHOS reverses all features of MGA back to baseline and reciprocally increases the numbers of Treg cells. Conclusions: The dual blockade of LIGHT and OXPHOS constitutes a promising target for clinical interventions in human MGA, possibly extending to other Th17-driven fibrotic diseases.
• Alcohol-induced suppression of miR-1948-3p promotes an adaptive HIF-1α response to limit hepatic steatosis
  GSE352328Mus musculus8 个样本2026-10-30

  To investigate the role of HIF-1α in alcohol-associated liver disease, we performed transcriptomic profiling on liver tissues from chronic alcohol-fed mice (AF) and mice with hepatocyte-specific Hif-1α knockdown (AF+Hif-1α KD). RNA-seq analysis revealed that Hif-1α deficiency markedly altered the hepatic transcriptional landscape and identified the disruption of the PPAR signaling pathway. Overall, this dataset provides insights into the molecular mechanisms by which HIF-1α limits hepatic steatosis during alcohol exposure.
• Heterogeneity and interaction of microglia and macrophages after retinal detachment
  GSE351957Mus musculus5 个样本2026-10-30

  This study aims to systematically investigate the evolutionary processes of microglia and macrophages during the onset and progression of retinal detachment (RD).
• Single-cell RNA sequencing of pooled orthotopic pancreatic tumors derived from PKM2-WT and PKM2-K89R cells
  GSE351631Mus musculus2 个样本2026-10-30

  We performed single-cell RNA sequencing of orthotopic pancreatic tumors established in NCG mice using pancreatic cancer cells expressing wild-type PKM2 (PKM2-WT) or the lactylation-deficient PKM2 K89R mutant (PKM2-K89R). For each group, tumor tissues from five mice were pooled before single-cell library preparation, resulting in one library per group. The dataset was used to characterize the tumor microenvironment and compare cell-type composition and cellular transcriptional states between the PKM2-WT and PKM2-K89R groups, with particular focus on fibroblast and cancer-associated fibroblast (CAF) subpopulations.

  单细胞
• Inactivation of Irs1 in pericentral hepatocytes promotes lipid oxidation
  GSE349448Mus musculus4 个样本2026-10-30

  Hepatic metabolic zonation enables periportal (PP) and pericentral (PC) hepatocytes to perform distinct functions in glucose and lipid metabolism. Insulin signaling is also spatially organized across the liver lobule, but the transcriptional role of insulin signaling in PC hepatocytes remains incompletely understood. To define the gene-expression programs regulated by insulin signaling in PC hepatocytes, we generated mice with inducible PC-specific deletion of insulin receptor substrate 1 (Irs1) using Cyp1a2CreER (Irs1-Cyp1a2 mice). RNA sequencing was performed to compare liver gene-expression profiles between Irs1-Cyp1a2 mice and littermate controls. This dataset provides a transcriptomic resource for identifying pathways regulated by PC IRS1 signaling and for understanding how spatial insulin signaling contributes to hepatic glucose and lipid metabolism.

  空间转录组
• HFpEF HMDP: ventricular RNA-seq in an expanded BXD strain panel
  GSE348752Mus musculus194 个样本2026-10-30

  Systems genetics strategy across multiple Hybrid Mouse Diversity Panel (HMDP) cohorts. RNA sequencing of ventricles from HFpEF mice was performed primarily in an expanded panel of BXD strains, together with a small number of classic inbred strains. This submission represents the expanded BXD component of the HFpEF HMDP project.
• Early Pitx2 modulation of Fgf10 directs asymmetric lung morphology
  GSE347452Mus musculus8 个样本2026-10-30

  Both the molecular cascade establishing Left-Right asymmetric anatomy, including the transcription factor Pitx2, and the signaling pathways controlling branching morphogenesis of the lung (a Left-Right asymmetric process) have been intensively studied. However, the two have never been linked. We identify Fgf10 as a Pitx2-sensitive signal in the mesenchyme of the developing mouse lung. Pitx2 suppresses Fgf10 expression, making the right lung, which lacks Pitx2 expression, grow faster than the left during the budding stage. Modulating Fgf10 dosage in the left mesenchyme is sufficient to shift levels of epithelial proliferation and thereby alter lung budding asymmetry. Pitx2 activity during the earliest lung bud stages is sufficient to establish differences in the primary airway branches, leading to subsequent asymmetric branching patterns that eventually manifest as the left-right differences in lung morphology. Thus, Pitx2 converts left-right mesenchymal identity into organ asymmetry by quantitatively tuning Fgf10-dependent epithelial growth during early lung organogenesis.
• RNA-sequencing of brain endothelial cells from Slc1a1 endothelial cell conditional knockout mice and controls
  GSE346752Mus musculus8 个样本2026-10-30

  The goal of this study was to understand the transcriptional response of brain endothelial cells to a loss of brain endothelial Slc1a1 expression. Sample GSM10039984 (ECs, control, 3) and GSM10039987 (ECs, mutant, 4) were excluded from all published analyses because of separation from its group on principal component analysis. Final analyses used n = 3 per group. The excluded sample is included in this deposition for completeness.
• A CD4-lineage erythro-myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation [RNA-Seq]
  GSE345263Mus musculus10 个样本2026-10-30

  Tissue-resident macrophages originate from distinct developmental sources, but in adulthood, their replenishment is thought to depend exclusively on circulating monocytes. Here, we identify a previously unrecognized CD4-lineage erythro-myeloid progenitor, termed EMPROR (Erythro-Myeloid Progenitor), that resides in the adult bone marrow and defines an alternative pathway for generating macrophages. EMPROR cells are phenotypically and transcriptionally distinct from hematopoietic stem cells, common myeloid progenitors, and monocyte precursors. They lack expression of Csf1r and Ccr2 while expressing Cd4 and c-Kit. Single-cell RNA sequencing, RNA velocity analysis, and in vitro and in vivo lineage assays demonstrate a multilineage potential encompassing macrophage, neutrophil, megakaryocytic, and erythroid fates. In vivo, EMPROR cells efficiently generate perivascular and tumor-associated macrophages independently of CCR2-mediated monocyte recruitment, and also contribute to erythroid and granulocytic lineages under inflammatory and neoplastic conditions. Transcriptomic comparisons position EMPROR cells closest to embryonic erythro-myeloid progenitors, indicating that an embryonic-like erythro-myeloid program persists within the adult bone marrow. These findings expand current models of adult myelopoiesis and highlight a previously unappreciated developmental pathway that sustains macrophage diversity beyond the classical monocyte lineage.

  单细胞
• A CD4-lineage erythro-myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation [scRNA-Seq]
  GSE345262Mus musculus3 个样本2026-10-30

  Tissue-resident macrophages originate from distinct developmental sources, but in adulthood, their replenishment is thought to depend exclusively on circulating monocytes. Here, we identify a previously unrecognized CD4-lineage erythro-myeloid progenitor, termed EMPROR (Erythro-Myeloid Progenitor), that resides in the adult bone marrow and defines an alternative pathway for generating macrophages. EMPROR cells are phenotypically and transcriptionally distinct from hematopoietic stem cells, common myeloid progenitors, and monocyte precursors. They lack expression of Csf1r and Ccr2 while expressing Cd4 and c-Kit. Single-cell RNA sequencing, RNA velocity analysis, and in vitro and in vivo lineage assays demonstrate a multilineage potential encompassing macrophage, neutrophil, megakaryocytic, and erythroid fates. In vivo, EMPROR cells efficiently generate perivascular and tumor-associated macrophages independently of CCR2-mediated monocyte recruitment, and also contribute to erythroid and granulocytic lineages under inflammatory and neoplastic conditions. Transcriptomic comparisons position EMPROR cells closest to embryonic erythro-myeloid progenitors, indicating that an embryonic-like erythro-myeloid program persists within the adult bone marrow. These findings expand current models of adult myelopoiesis and highlight a previously unappreciated developmental pathway that sustains macrophage diversity beyond the classical monocyte lineage.

  单细胞
• A CD4-lineage erythro-myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation
  GSE345108Mus musculus12 个样本2026-10-30

  Tissue-resident macrophages originate from distinct developmental sources, but in adulthood, their replenishment is thought to depend exclusively on circulating monocytes. Here, we identify a previously unrecognized CD4-lineage erythro-myeloid progenitor, termed EMPROR (Erythro-Myeloid Progenitor), that resides in the adult bone marrow and defines an alternative pathway for generating macrophages. EMPROR cells are phenotypically and transcriptionally distinct from hematopoietic stem cells, common myeloid progenitors, and monocyte precursors. They lack expression of Csf1r and Ccr2 while expressing Cd4 and c-Kit. Single-cell RNA sequencing, RNA velocity analysis, and in vitro and in vivo lineage assays demonstrate a multilineage potential encompassing macrophage, neutrophil, megakaryocytic, and erythroid fates. In vivo, EMPROR cells efficiently generate perivascular and tumor-associated macrophages independently of CCR2-mediated monocyte recruitment, and also contribute to erythroid and granulocytic lineages under inflammatory and neoplastic conditions. Transcriptomic comparisons position EMPROR cells closest to embryonic erythro-myeloid progenitors, indicating that an embryonic-like erythro-myeloid program persists within the adult bone marrow. These findings expand current models of adult myelopoiesis and highlight a previously unappreciated developmental pathway that sustains macrophage diversity beyond the classical monocyte lineage.

  单细胞
• Transcriptional response of J774A.1 macrophages to a monoacylglycerol mixture, oleic acid, or palmitic acid
  GSE345076Mus musculus24 个样本2026-10-30

  Monoacylglycerols (MAGs) accumulate in adipose tissue macrophages, but whether macrophages respond to MAGs differently than to free fatty acids is not established. To determine the concentration at which murine J774A.1 macrophages mount a transcriptional response to these lipids, cells were treated for 24 h with a commercial monoacylglycerol mixture, oleic acid, or palmitic acid at 500 uM or 5 mM and profiled by bulk RNA sequencing. At 5 mM, the MAG mixture altered a small set of genes that changed concordantly with oleic acid and included the lipid droplet protein Plin2 and the fatty acid oxidation gene Cpt1a, whereas palmitic acid induced inflammatory transcripts including Il1b and Trem1 with essentially no overlap with the MAG mixture. These data indicate that monoacylglycerols in this mixture engage a lipid handling program rather than an inflammatory one in macrophages.
• The pyrin inflammasome senses OCTN2-mediated uptake of extracellular ʟ-carnitine from muscle injury or ingestion
  GSE343742Mus musculus12 个样本2026-10-30

  Red-meat-containing diets are epidemiologically associated with diseases of chronic inflammation, while diets that restrict red meat improve health. Yet, it is uncertain how red meat incites inflammation. Here, we discover that ʟ-carnitine, an amino acid highly concentrated in skeletal muscle myocytes, drives inflammasome activation in lipopolysaccharide (LPS)-challenged mice and LPS-primed murine and human macrophages. We find that extracellular ʟ-carnitine represses mevalonate synthesis, thereby triggering activation of the pyrin inflammasome, downstream of cellular import by the high-affinity ʟ-carnitine transporter OCTN2. We find that the inflammatory response to skeletal muscle injury also requires pyrin and OCTN2. Thus, in summary, we identify macrophages as sentinels of exogenous and endogenous extracellular ʟ-carnitine that serve as a proxy for skeletal myocyte damage, and we open the field to examine the mechanistic basis for how excess dietary intake of carnitine-rich food drives inflammatory disease.
• FGF12 and FGF13 promote atrial rhythm homeostasis
  GSE334673Mus musculus16 个样本2026-10-30

  Data from human and mouse studies of atrial fibrillation implicate FGF12/13 in atrial fibrillation. To determine if FGF12 and FGF13 regulate atrial rhythm homeostasis, we inactivated them in mouse aCMs. Serial EKG analysis revealed that dual Fgf12/13 inactivation results in AF.
• Lidocaine attenuates LPS-induced macrophage inflammation through transcriptomic reprogramming and inhibition of NF-κB/STAT1 signaling
  GSE329186Mus musculus12 个样本2026-10-30

  Lidocaine has been increasingly recognized for its anti-inflammatory and immunomodulatory properties, but the global transcriptional mechanisms remain unclear. In this study, RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) and treated with lidocaine at different concentrations. RNA sequencing was performed to characterize transcriptomic alterations induced by lidocaine. Lidocaine significantly reduced LPS-induced secretion of TNF-α and IL-6, partially reversed inflammatory gene expression programs, and suppressed multiple inflammation-related pathways, including TNFα signaling via NF-κB, interferon responses, inflammatory response, and IL6/JAK/STAT signaling. Further validation confirmed reduced expression of Il6, Tnf, Il1b, and Nos2, inhibition of p65 and STAT1 phosphorylation, and downregulation of iNOS. These findings demonstrate that lidocaine attenuates macrophage inflammatory responses through coordinated transcriptional reprogramming and suppression of NF-κB/STAT1 signaling.
• T cell-derived IL-17A deteriorates periodontium under insulin resistance
  GSE327375Mus musculus12 个样本2026-10-30

  Insulin resistance (IR) is a systemic metabolic disorder associated with chronic inflammatory diseases, yet the immune-molecular mechanisms by which IR exacerbates periodontitis remain elusive. This study aimed to investigate the role of T cell-derived interleukin (IL) -17A in IR-aggravated periodontitis and the underlying mechanisms. A total of 4948 participants aged ≥30 years from the National Health and Nutrition Examination Survey 2009–2014 were included to assess the clinical association between IR and periodontitis. A murine model of IR combined with periodontitis was established. Il17a⁻/⁻ mice and FTY720 were used to verify the function of IL-17A and CD4⁺ T cell migration. Bulk RNA sequencing, flow cytometry, immunofluorescence, micro-computed tomography (micro-CT), and histological staining were performed to characterize immune cell infiltration and periodontium destruction. Primary mouse gingival fibroblasts (GFs) were isolated to explore the effects of IL-17A on inflammatory responses and collagen metabolism. The results demonstrated that IR was an independent risk factor for periodontitis at the population level (Odds Ratio=1.22, 95% CI 1.06–1.41) and significantly exacerbated alveolar bone loss and collagen degradation in the mouse model. IR-aggravated periodontitis was accompanied by increased gingival infiltration of CD4⁺ T cells and elevated IL-17A expression, with IL-17A primarily secreted by cervical lymph node-derived CD4⁺ T cells. Il17a⁻/⁻ and FTY720 treatment alleviated periodontium destruction and reduced gingival immune cell infiltration. Furthermore, the recombinant IL-17A upregulated the expression of pro-inflammatory genes (Il6, Il1β, Tnfa) and the collagen-degrading enzyme gene Mmp3, downregulated the collagen synthesis gene Col1a1, and inhibited the migration of GFs via the NF-κB signalling pathway. In conclusion, IL-17A secreted by cervical lymph node-derived CD4⁺ T cells promotes IR-aggravated periodontium destruction, by regulating the periodontal immune microenvironment and modulating GFs function. These findings identified IL-17A as a potential therapeutic target for periodontitis in patients with IR.
• NFYA regulates spermatogenesis through multifaceted chromatin interactions
  GSE326586Mus musculus22 个样本2026-10-30

  During spermatogenesis, germ cells undergo extensive chromatin remodeling to promote highly diverse and stage-specific transcriptional programs that drive differentiation, meiosis, and spermiogenesis. However, conventional loss-of-function approaches do not allow systematic interrogation of gene function across spermatogenesis in vivo. Here, we introduce a protein-degron strategy coupled with intra-seminiferous tubule injection (dTAG-IS) to enable rapid, simultaneous, and stage-resolved functional investigation of NFYA during spermatogenesis. Acute NFYA-depletion induces apoptosis in differentiating spermatogonia (diff-Spg), pachytene spermatocytes (pSpc), and round spermatids (rStd), revealing an essential requirement across spermatogenesis. Mechanistically, NFYA exhibits stage-specific chromatin-binding patterns and directly regulates distinct transcriptional programs, including cell cycle progression and histone assembly in diff-Spg; chromosome organization and DNA damage response in pSpc; and antioxidative stress programs in rStd. Together, our study underscores dTAG-IS as a versatile strategy for in vivo loss-of-function studies during spermatogenesis and establishes NFYA as a multifaceted regulator that drives stage-specific transcriptional programs to ensure spermatogenesis progression.
• CRYAB-driven mitochondrial fission induces senescence to promote adaptive resistance to EGFR-TKI in LUAD brain metastasis
  GSE326531Mus musculus4 个样本2026-10-30

  Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) exhibit limited efficacy against lung cancer brain metastases, often resulting in rapid and inevitable resistance. However, the unique mechanisms driving this brain microenvironment-specific therapeutic failure remain elusive. Here, utilizing in vivo orthotopic models and single-cell RNA sequencing, we reveal that targeted therapy induces a distinct, metabolically hyperactive senescent cell subpopulation that drives rapid EGFR-TKI tolerance in brain metastasis. We identify the molecular chaperone CRYAB as an indispensable driver specifically upregulated within this senescent persister state. Mechanistically, CRYAB physically interacts with VDAC2 at the outer mitochondrial membrane, promoting endoplasmic reticulum (ER)-mitochondria tethering and calcium influx. This CRYAB-VDAC2 axis orchestrates adaptive mitochondrial fission, hyperactivating oxidative metabolism while simultaneously shielding（preventing？） senescent cells from fatal oxidative stress. Genetic or pharmacological blockade of mitochondrial fission completely abolishes CRYAB-mediated therapeutic resistance. Therapeutically, we demonstrate that a 25-hydroxycholesterol (25HC) dietary intervention acts as a potent in vivo senolytic strategy, directly dismantling the CRYAB-dependent resistance network, eradicating senescent persister cells, and synergistically prolonging overall survival when combined with Osi. Furthermore, high baseline CRYAB expression in pre-treatment primary lung biopsies clinically predicts lower intracranial objective response rates and shorter progression-free survival in a cohort of advanced EGFR-mutant NSCLC patients. Collectively, our study uncovers a novel CRYAB-VDAC2-mitochondrial fission axis that enforces therapy-induced senescence and highlights 25HC dietary intervention as a highly translatable combinatorial strategy to overcome EGFR-TKI resistance in brain metastasis.

  单细胞
• Tissue Nano-Transfection Promotes Vascularization to Enhance Acellular Nerve Allograft–Mediated Nerve Repair [RNAseq_invitro_ANAs]
  GSE324287Mus musculus16 个样本2026-10-30

  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.
• CAR-DC1s drive polyclonal neoantigen-specific immunity
  GSE319838Mus musculus16 个样本2026-10-30

  CAR therapies typically target single antigens, limiting recognition and favoring tumour escape. Conversely, type 1 conventional dendritic cells (DC1s) are specialized to cross-prime diverse T-cell responses, but lack the pathogen-derived signals required for strong activation in "self"-derived tumors. Efforts to hard-wire such signals using CARs in DC1s have remained elusive, in part due to a lineage-specific constraint on stable, high-level CAR surface expression. Here, we show that replacing conventional antibody fragments with single-domain nanobodies overcomes this DC1–specific constraint and enables construction of tumour-targeted receptors with high surface density. By systematically optimizing TLR4-derived elements within this scaffold, we developed a receptor that couples tumor engagement to TLR signaling, markedly enhancing activation, capture and cross-presentation of endogenous antigens. In a heterogeneous syngeneic sarcoma model, CAR-DC1s induce complete tumor rejection and durable memory. Integrating mass spectrometry of the cross-presented tumour immunopeptidome with tetramer staining, single-cell RNA sequencing paired with TCR sequencing, and adoptive transfer, we show that CAR-DC1s imprint a stem-like transcriptional programme on newly primed T-cells and expand a polyclonal, recall-competent tumour-specific repertoire, thereby reprogramming the quality and breadth of anti-tumour immunity against endogenous neoantigen in vivo.

  单细胞
• FACT depletion results in a temporal cascade of chromatin disruption preceding transcriptional dysfunction in stem cells [CUT&Run]
  GSE319809Mus musculus193 个样本2026-10-30

  The histone chaperone FACT is essential for chromatin organization and stem cell identity, yet how it preserves chromatin integrity over time remains unclear. We generated a high-resolution temporal map of events leading to chromatin destabilization and cell identity loss in murine embryonic stem cells following rapid dTAG-mediated depletion of FACT. Loss of FACT initiates a rapid cascade, with loss of H3K4me3 and disruption of nucleosome phasing at the 5′ ends of active genes beginning within 10 minutes. This architectural destabilization permits pluripotency transcription factors to ectopically occupy gene bodies in a transcription-dependent manner. Epigenomic disruptions result in stalled RNA Polymerase II occupancy and altered H3K36me3 deposition preceding a global transcriptional collapse at 2 hours of FACT depletion. Together, these findings define a temporal hierarchy in which epigenomic failure precedes and drives transcriptional dysfunction, revealing that continuous FACT activity is required to prevent progressive deterioration of chromatin architecture.
• Immune cells adapt to distinct stem cell niches to govern tissue homeostasis [scRNA-seq]
  GSE314679Mus musculus2 个样本2026-10-30

  In adult tissues, epithelial stem cells exist within distinct residences, each endowing them with exclusive instructions for regenerative fitness in homeostasis and wound repair. Key components of these ‘niches’ are immune cells, which protect the host against external and internal threats. Whether and how stem cell: immune cell crosstalk contributes to normal tissue homeostasis remains less clear. Here, we discover functional adaptation of lymphocytes within two distinct skin stem cell niches and show that through this communication, each niche adjusts to meet diverse tissue demands. In the upper hair follicle, where microbial load is high, T cells express lymphotoxin-β and stimulate adjacent receptor-positive epithelial stem cells to form an immune-competent niche tailored to control microbial expansion. By contrast, in the epidermis, these T cells produce amphiregulin to maintain stem cell stoking of the skin’s barrier. Concomitantly, they express the immune checkpoint protein ‘LAG3’, which autorestricts lymphocyte numbers, and hence amphiregulin levels, thereby preventing over-proliferative responses. Finally, when epidermal T cells are absent, distinct dermal lymphocytes restore the imbalance by colonizing the niche and activating amphiregulin. Our findings unveil new modes of homeostatic control and functional specialization of immune-stem cell niches, tailoring them to suit the demands of distinct tissue microenvironments.

  单细胞
• Immune cells adapt to distinct stem cell niches to govern tissue homeostasis [bulkRNA-seq]
  GSE314678Mus musculus4 个样本2026-10-30

  In adult tissues, epithelial stem cells exist within distinct residences, each endowing them with exclusive instructions for regenerative fitness in homeostasis and wound repair. Key components of these ‘niches’ are immune cells, which protect the host against external and internal threats. Whether and how stem cell: immune cell crosstalk contributes to normal tissue homeostasis remains less clear. Here, we discover functional adaptation of lymphocytes within two distinct skin stem cell niches and show that through this communication, each niche adjusts to meet diverse tissue demands. In the upper hair follicle, where microbial load is high, T cells express lymphotoxin-β and stimulate adjacent receptor-positive epithelial stem cells to form an immune-competent niche tailored to control microbial expansion. By contrast, in the epidermis, these T cells produce amphiregulin to maintain stem cell stoking of the skin’s barrier. Concomitantly, they express the immune checkpoint protein ‘LAG3’, which autorestricts lymphocyte numbers, and hence amphiregulin levels, thereby preventing over-proliferative responses. Finally, when epidermal T cells are absent, distinct dermal lymphocytes restore the imbalance by colonizing the niche and activating amphiregulin. Our findings unveil new modes of homeostatic control and functional specialization of immune-stem cell niches, tailoring them to suit the demands of distinct tissue microenvironments.
• Acute Degradation of Pumilio Proteins Reveals a Biphasic Posttranscriptional Regulatory Hierarchy in Embryonic Stem Cell Fate Decision [RNA-Seq]
  GSE310694Mus musculus84 个样本2026-10-30

  Post-transcriptional regulation is critical for mammalian embryogenesis yet has been underexplored. We previously showed that RNA-binding Pumilio proteins (Pum1/2) are essential for early mouse embryogenesis and embryonic stem cell (ESC) functions. Here, using acute protein degradation systems combined with time-resolved RNA-seq and eCLIP, we delineate a two-phase regulatory hierarchy modulated by Pum1/2 in mouse ESCs. The first phase, occurring within 10 hours of Pum1/2 depletion, is predominantly the stabilization of over 100 Pum1/2-target mRNAs, while the second phase, occurring in subsequent 66 hours, propagates to over 1,000 mRNAs mostly through indirect regulatory effects. Functionally, Pum1/2 depletion delays transition from naïve to formative pluripotency, impairs neuroectoderm differentiation, and enhances germline specification. Mechanistically, Pum1/2 directly repress mRNAs encoding PRC2 subunits, including Suz12, thereby constraining H3K27me3 deposition at neuroectodermal gene loci. These findings establish Pum1/2 as biphasic post-transcriptional regulators of pluripotency and lineage balance and link RNA stability control to chromatin-mediated silencing.
• Acute Degradation of Pumilio Proteins Reveals a Biphasic Posttranscriptional Regulatory Hierarchy in Embryonic Stem Cell Fate Decision [iCLIP]
  GSE310693Mus musculus8 个样本2026-10-30

  Post-transcriptional regulation is critical for mammalian embryogenesis yet has been underexplored. We previously showed that RNA-binding Pumilio proteins (Pum1/2) are essential for early mouse embryogenesis and embryonic stem cell (ESC) functions. Here, using acute protein degradation systems combined with time-resolved RNA-seq and eCLIP, we delineate a two-phase regulatory hierarchy modulated by Pum1/2 in mouse ESCs. The first phase, occurring within 10 hours of Pum1/2 depletion, is predominantly the stabilization of over 100 Pum1/2-target mRNAs, while the second phase, occurring in subsequent 66 hours, propagates to over 1,000 mRNAs mostly through indirect regulatory effects. Functionally, Pum1/2 depletion delays transition from naïve to formative pluripotency, impairs neuroectoderm differentiation, and enhances germline specification. Mechanistically, Pum1/2 directly repress mRNAs encoding PRC2 subunits, including Suz12, thereby constraining H3K27me3 deposition at neuroectodermal gene loci. These findings establish Pum1/2 as biphasic post-transcriptional regulators of pluripotency and lineage balance and link RNA stability control to chromatin-mediated silencing.
• Ribosomal modification by BUD23 drives selective translational control over energy state and metabolic health [Ribo-seq]
  GSE308616Mus musculus4 个样本2026-10-30

  Efficient energy metabolism is essential for health, and its dysregulation drives cardiometabolic disease. Delivery of regulatory control through translation and ribosome function is emerging as important. Here, we identify the rRNA methyltransferase BUD23 as a potent regulator of cellular and systemic energy homeostasis. Adipocyte-specific deletion of BUD23 in mice regulates lipid and mitochondrial metabolism resulting in a pronounced lean phenotype and resistance to diet-induced obesity. Mechanistically, BUD23 modulates translation initiation and efficiency of mRNAs with specific features – including short 5’ UTR length and GC-rich post-initiation codon usage – characteristic of mitochondrial and lipogenic proteins.Together, our findings uncover a conserved translational control mechanism that regulates energy state in cellular metabolism.
• Ribosomal modification by BUD23 drives selective translational control over energy state and metabolic health
  GSE308532Mus musculus9 个样本2026-10-30

  Efficient energy metabolism is essential for health, and its dysregulation drives conditions like cardiometabolic disease and obesity. Delivery of regulatory control through translation and ribosome function is emerging as important. Here, we identify the rRNA methyltransferase BUD23 as a potent regulator of cellular and systemic energy homeostasis. Adipocyte-specific deletion of BUD23 in mice regulates lipid and mitochondrial metabolism resulting in a pronounced lean phenotype and resistance to diet-induced obesity. Mechanistically, BUD23 modulates translation initiation and efficiency of mRNAs with specific features – including short 5’ UTR length and GC-rich post-initiation codon usage - characteristic of mitochondrial and lipogenic proteins. Human genetic analyses and drug-target Mendelian Randomisation support a role for BUD23 in cardiometabolic traits and diseases. Together, our findings uncover a conserved translational control mechanism that regulates energy metabolism and offers a potential therapeutic target.
• Ribosomal modification by BUD23 drives selective translational control over energy state and metabolic health
  GSE308207Mus musculus16 个样本2026-10-30

  Efficient energy metabolism is essential for health, and its dysregulation drives conditions like cardiometabolic disease and obesity. Delivery of regulatory control through translation and ribosome function is emerging as important. Here, we identify the rRNA methyltransferase BUD23 as a potent regulator of cellular and systemic energy homeostasis. Adipocyte-specific deletion of BUD23 in mice regulates lipid and mitochondrial metabolism resulting in a pronounced lean phenotype and resistance to diet-induced obesity. Mechanistically, BUD23 modulates translation initiation and efficiency of mRNAs with specific features – including short 5’ UTR length and GC-rich post-initiation codon usage - characteristic of mitochondrial and lipogenic proteins. Human genetic analyses and drug-target Mendelian Randomisation support a role for BUD23 in cardiometabolic traits and diseases. Together, our findings uncover a conserved translational control mechanism that regulates energy metabolism and offers a potential therapeutic target.
• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [Embryo_Stranded_RNAseq]
  GSE307084Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.
• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [ATAC-Seq]
  GSE306939Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.