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。

• Late-gestation heat stress induces Gene Expression changes in the mammary gland parenchyma at birth and weaning [RNA-Seq]
  GSE345863Bos taurus32 个样本2026-10-30

  In utero heat stress during late gestation can alter development of the fetal mammary gland, potentially through changes in gene ex[ression. Whether such expression changes persist after birth is not well characterized. Here, RNA-seq was used to profile thegene expression in the mammary gland parenchyma from Holstein heifer calves born to dams exposed to heat stress (HT) or active cooling (CL) during late gestation. Mammary gland Parenchyma tissue was collected after euthanasia were collected at two timepoints, birth and weaning, to assess gene expression differences between in utero environments and how they change across early development.
• Late-gestation heat stress induces persistent DNA methylation changes in the mammary gland parenchyma at birth and weaning [Bisulfite-Seq]
  GSE345861Bos taurus32 个样本2026-10-30

  In utero heat stress during late gestation can alter development of the fetal mammary gland, potentially through changes in DNA methylation. Whether such epigenetic changes persist after birth is not well characterized. Here, whole-genome bisulfite sequencing (WGBS) was used to profile the DNA methylome of mammary gland parenchyma from F1 Holstein heifer calves born to dams exposed to heat stress (HT) or active cooling (CL) during late gestation. Mammary gland Parenchyma tissue was collected after euthanasia were collected at two timepoints, birth and weaning, to assess methylation differences between in utero environments and how they change across early development.
• 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
  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.
• Small RNA sequencing reveals hepatic miRNA signatures associated with metabolic dysfunction-associated steatohepatitis in cynomolgus monkeys
  GSE341556Macaca fascicularis13 个样本2026-10-30

  Small RNA sequencing was performed on liver tissues from cynomolgus monkeys with healthy control status, metabolic dysfunction-associated steatohepatitis (MASH), and DT109-treated MASH. This study aimed to characterize hepatic small RNA expression profiles associated with MASH and provide a resource for investigating disease-associated miRNA alterations.
• Catabolite Activator Protein and quorum sensing cross-control group behaviors in Vibrio campbellii
  GSE341290Vibrio campbellii ATCC BAA-111636 个样本2026-10-30

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Catabolite Activator Protein and quorum sensing cross-control group behaviors in Vibrio campbellii [ChIP-Seq]
  GSE341289Vibrio campbellii ATCC BAA-111624 个样本2026-10-30

  Vibrio species adapt to different niches by sensing and responding to environmental signals such as nutrients, host cues, and quorum sensing autoinducers. Vibrio campbellii uses the master quorum sensing transcription factor LuxR to control expression of hundreds of genes at high cell density. Furthermore, many gamma-proteobacteria use the global transcription factor Catabolite Activator Protein (CAP) to control numerous physiologically relevant pathways, many of which are also modulated by quorum sensing, such as competence, biofilm formation, and carbon metabolism. However, the extent to which these two global transcription factors overlap to co-regulate gene expression and bacterial behaviors is understudied. In this study, we used Chromatin Immunoprecipitation-sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) to determine the individual and combined regulons of CAP and LuxR in V. campbellii. We found that CAP and LuxR co-occupied 11 promoters to synergistically or antagonistically co-regulate genes involved with metabolism, respiration, and virulence. It was previously proposed that CAP and LuxR both bound the bioluminescence (luxCDABE) promoter to co-regulate these genes, and our RNA-seq data showed that these were indeed the most strongly co-regulated genes. However, our ChIP-seq data revealed that only LuxR bound the luxCDABE promoter in vivo. This pattern of co-regulation – where both CAP and LuxR strongly impact transcription but only LuxR binds the promoter – was the most common mechanism observed. Our model for bioluminescence regulation is that CAP indirectly activates luxCDABE expression through the regulation of an intermediate factor. This study established new connections between the global gene regulatory networks underpinning nutrient sensing and population sensing.
• Catabolite Activator Protein and quorum sensing cross-control group behaviors in Vibrio campbellii [RNA-seq]
  GSE339401Vibrio campbellii ATCC BAA-111612 个样本2026-10-30

  Vibrio species adapt to different niches by sensing and responding to environmental signals such as nutrients, host cues, and quorum sensing autoinducers. Vibrio campbellii uses the master quorum sensing transcription factor LuxR to control expression of hundreds of genes at high cell density. Furthermore, many gamma-proteobacteria use the global transcription factor Catabolite Activator Protein (CAP) to control numerous physiologically relevant pathways, many of which are also modulated by quorum sensing, such as competence, biofilm formation, and carbon metabolism. However, the extent to which these two global transcription factors overlap to co-regulate gene expression and bacterial behaviors is understudied. In this study, we used Chromatin Immunoprecipitation-sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) to determine the individual and combined regulons of CAP and LuxR in V. campbellii. We found that CAP and LuxR co-occupied 11 promoters to synergistically or antagonistically co-regulate genes involved with metabolism, respiration, and virulence. It was previously proposed that CAP and LuxR both bound the bioluminescence (luxCDABE) promoter to co-regulate these genes, and our RNA-seq data showed that these were indeed the most strongly co-regulated genes. However, our ChIP-seq data revealed that only LuxR bound the luxCDABE promoter in vivo. This pattern of co-regulation – where both CAP and LuxR strongly impact transcription but only LuxR binds the promoter – was the most common mechanism observed. Our model for bioluminescence regulation is that CAP indirectly activates luxCDABE expression through the regulation of an intermediate factor. This study established new connections between the global gene regulatory networks underpinning nutrient sensing and population sensing.
• 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.
• Variable Imprinting of Hepatitis C Virus-Induced Chromatin Remodeling Following Viral Clearance [ChIP-Seq]
  GSE333673Homo sapiens49 个样本2026-10-30

  Background & Aims: Direct-acting antivirals (DAAs) have revolutionized Hepatitis C virus (HCV) care, allowing for high cure rates. However, the risk of Hepatocellular carcinoma (HCC) persists in a subset of patients even after sustained virologic response (SVR). Understanding the factors linking HCV infection to HCC risk, both before and after cure, may reveal novel HCC prevention strategies. We previously identified an HCV-induced ""epigenetic scar"" that can persist despite viral cure. Currently, it is unknown whether this epigenetic signature persists across all cured patients or if it exhibits significant inter-patient variability. This study aimed to characterize the heterogeneity of epigenetic reversion following SVR and to investigate whether the kinetics of viral clearance is a mechanism that is associated with this heterogeneity, by comparing different treatment regimens. Methods: To precisely evaluate epigenetic reversion while controlling for significant inter-patient variability in baseline chromatin landscapes, we analyzed a unique cohort of paired human liver biopsies (pre- and post-SVR) from patients treated with IFN-based therapies. To explore potential drivers of the observed heterogeneity, we utilized cell culture models treated with DAAs or varying concentrations of IFN to mimic rapid versus gradual viral elimination. Genome-wide H3K9ac ChIP-seq and RNA-seq were performed to characterize epigenetic and transcriptomic changes. The results were also validated with another histone modification, H3K27Ac, from HCV patients treated with IFN and DAA. Results: By normalizing post-treatment profiles to each patient's own baseline, we revealed heterogeneity in the trajectory of recovery. While some patients achieved extensive reversion of HCV-induced signatures, others retained a persistent H3K9ac footprint despite viral clearance. In cell culture models, distinct remodeling patterns were observed based on treatment kinetics: regimens inducing rapid viral clearance (DAA treatment or high-concentration IFN) were associated with greater persistence of the epigenetic signature. Conversely, gradual clearance (low-concentration IFN) coincided with more extensive reversion of H3K9ac modifications. Independent clinical validation confirmed these dynamics, showing that DAA-cured patients harbor a significantly stronger persistent H3K27ac signature compared to those cured by IFN. Conclusions: These results indicate that the host epigenome possesses a variable capacity for recovery that is distinct from virologic outcomes. Our data suggests that the kinetics of viral clearance may be a key determinant of this epigenetic plasticity, highlighting the need to look beyond SVR to understand the residual oncogenic environment of the cured liver.
• 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.
• Aberrant stabilization of the m6A reader IGF2BP3 drives metastatic progression and 5-FU refractoriness in FBXW7-mutant colorectal cancer
  GSE327329Homo sapiens13 个样本2026-10-30

  FBXW7 is mutated in approximately 10% of colorectal cancers (CRC), and the vast majority of these alterations are loss-of-function mutations that abrogate its E3 ligase activity. Tumors harboring FBXW7 mutations frequently display aggressive clinical behavior, including enhanced metastatic dissemination and poor response to chemotherapy. However, the post-transcriptional regulatory axis downstream of FBXW7 loss has remained largely unexplored. In this study, we aimed to delineate the mechanistic link between FBXW7-dependent alterations in m6A RNA methylation and malignant phenotypic outcomes in CRC. We found that loss of FBXW7 markedly increased the protein abundance of the m6A reader IGF2BP3, and this effect was attributable to impaired GSK3β/FBXW7-dependent degradation of IGF2BP3. Mechanistically, FBXW7 promoted K63‐linked polyubiquitination and autophagy-mediated degradation of IGF2BP3, indicating that FBXW7 serves as a post-translational brake on IGF2BP3 stability. In FBXW7-deficient cells, IGF2BP3 preferentially bound cancer-promoting transcripts, including DPYD and COL4A1, and stabilized these mRNAs in an m6A-dependent manner. Functionally, IGF2BP3-mediated stabilization of DPYD and COL4A1 promoted epithelial to mesenchymal transition and increased resistance to 5-FU. In vivo, knockout of IGF2BP3 in FBXW7-deficient CRC models significantly reduced liver metastasis and chemoresistance to 5-FU, demonstrating that IGF2BP3 is a critical effector of the FBXW7-m6A axis. Collectively, these findings establish IGF2BP3 as a previously unrecognized post-transcriptional driver of metastasis and 5-FU refractoriness in FBXW7-mutant CRC, and suggest that therapeutic strategies aimed at disrupting IGF2BP3 stabilization or m6A-dependent IGF2BP3-mRNA interactions provides a rationale for therapeutic intervention in FBXW7-mutated CRC.
• 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.
• 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
• Cucumber-derived exosome-like nanovesicles promote diabetic wound healing via AKT-HO-1 signaling
  GSE318192Homo sapiens10 个样本2026-10-30

  This study investigates the therapeutic efficacy of Cucumis sativus-derived exosome-like nanovesicles (CELNs) in promoting diabetic wound healing. We identified CELNs as a superior candidate among Cucurbitaceae species for enhancing fibroblast function and modulating the wound microenvironment. RNA-seq analysis of CELN-treated human dermal fibroblasts reveals a significant upregulation of epigen (EPGN) and activation of the NRF2-mediated antioxidant pathway. Mechanistically, CELNs activate the EGFR–PI3K/AKT–NRF2 axis, which mitigates oxidative stress and accelerates cellular migration and proliferation. To ensure sustained delivery, a CELN-loaded hydrogel system was developed, which significantly enhanced re-epithelialization and collagen deposition in STZ-induced diabetic mice. Our findings demonstrate that CELNs offer a promising nanotherapeutic approach for managing chronic diabetic ulcers by targeting EGFR-mediated antioxidant signaling.
• Modeling Progressive Pseudorheumatoid Arthropathy of Childhood: Disease Progression and Cartilage Pathology in CCN6 Deficient Sheep
  GSE317805Ovis aries34 个样本2026-10-30

  Progressive Pseudorheumatoid Arthropathy of Childhood (PPAC) is a rare, autosomal recessive disorder caused by loss-of-function mutations in Cellular Communication Network Factor 6 (CCN6). Patients with PPAC present asymptomatic at birth but develop polyarticular arthropathy throughout childhood, often requiring multiple arthroplasties before age 30. Currently, no therapies exist to prevent or delay PPAC progression. Furthermore, the role of CCN6 in joint development and homeostasis is unknown due to the limited availability of pre-symptomatic patient tissue and the absence of any PPAC phenotype in Ccn6 knockout (KO) mice. CCN6 knockout sheep were generated, anticipating that a larger and longer-lived animal would better model human PPAC. We found that KO sheep were clinically indistinguishable from wild-type (WT) flock mates at birth but developed signs of joint disease that progressed with age. Macroscopic and histologic examination of KO tissues revealed evidence of cartilage damage that was absent in WT animals. KO and WT cartilage also differed transcriptomically, with KO sheep cartilage gene expression sharing multiple features observed in cartilage derived from PPAC-patient induced pluripotent cell lines. These data demonstrate that CCN6 knockout sheep recapitulate the key clinical, histological, and molecular features of human PPAC, establishing this model as a valuable platform for elucidating disease mechanisms and testing potential therapies.
• RNA-seq and CRISPR screen after venetoclax and azacitidine treatment in AML cells
  GSE314299Homo sapiens30 个样本2026-10-30

  This SuperSeries is composed of the SubSeries listed below.

  扰动筛选SuperSeries
• The p38α MAPK-MK2 axis drives chemotherapy-mediated nuclear actin remodeling to promote ovarian cancer progression
  GSE311931Homo sapiens18 个样本2026-10-30

  We sequenced SKOV3 (EV), wild-type, and R62D cells treated with or without cisplatin.It is to figure out whether cisplatin and nuclear F-actin levels would affect the transcriptional profile.
• 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.
• Transcriptomic response to TRIP12 knockdown and HSP90 inhibition in melanoma cells
  GSE306539Homo sapiens32 个样本2026-10-30

  Melanoma, as a typical cancer, is characterized by high mutational burden and rapid proliferation, both of which contribute to elevated proteotoxic stress and reliance on protein quality control systems. To model this, we used the melanoma cell lines Ma-Mel-102 (differentiated, MLANA- and MITF-expressing, ~1200 missense mutations) and Ma-Mel-94 (dedifferentiated, ~700 missense mutations). This study investigates the role of the E3 ubiquitin ligase TRIP12 in regulating proteostasis in melanoma, particularly under proteotoxic stress induced by inhibition of HSP90, a key molecular chaperone. This dataset provides RNA-seq transcriptomic profiles of Ma-Mel-94 and Ma-Mel-102 cells following siRNA-mediated TRIP12 knockdown, with or without HSP90 inhibition by 17-DMAG.
• HOXA9 reprograms 3D genome architecture to regulate oncogenic transcription in acute myeloid leukemia [CUT&RUN]
  GSE301083Homo sapiens31 个样本2026-10-30

  The hierarchical three-dimensional (3D) organization of chromatin underpins the spatial and temporal control of gene expression during development. This principle is exemplified by the Hox gene clusters, where dynamic topological architecture governs precise transcriptional activation. While disruption of chromatin organization at Hox genes is increasingly recognized in various human malignancies, the extent to which Hox genes themselves contribute to shaping 3D genome architecture remains poorly understood. In particular, it is unknown whether oncogenic overexpression of HOXA9—a highly conserved transcription factor and common downstream effector of diverse genetic alterations in acute myeloid leukemia (AML)—can actively reprogram chromatin topology. Here, we uncover a pivotal role for HOXA9 as a master regulator of 3D chromatin architecture in human AML. We demonstrate that HOXA9 orchestrates a leukemia-specific reconfiguration of chromatin topology. HOXA9 promotes the formation of leukemia specific topologically associating domains (TADs) and establishes long-range enhancer–promoter interactions essential for maintaining the leukemic transcriptional program. Perturbation of HOXA9 leads to widespread architectural collapse, marked by the dissolution of chromatin loops, disrupted enhancer communication, and silencing of critical leukemogenic genes. Furthermore, HOXA9-mediated chromatin looping occurs independently of CTCF. Instead, HOXA9 functions through the cohesin complex to facilitate higher-order genome organization, thereby functioning as a non-canonical architectural factor. Among its targets, we identify NHLRC2 as a HOXA9-associated loop gene essential for leukemic cell survival and proliferation. Collectively, these findings uncover a previously unappreciated architectural function of HOXA9 in modulating 3D genome organization and sustaining oncogenic gene expression in AML. More broadly, they suggest a mechanistic paradigm in which HOX transcription factors actively reprogram nuclear architecture to enforce lineage-specific or malignant gene expression programs.

  空间转录组扰动筛选
• Gene expression profile and TCR-sequencing at single-cell level of PBMCs responding to EBV after 6 days of in vitro incubation.
  GSE277638Homo sapiens24 个样本2026-10-30

  In this work, we were able to establish a protocol for PBMC infection and sequence, for the first time at a single-cell level, the transcriptome of all cells capable of responding to the Epstein-Barr virus in healthy individuals and in certain patients with Inborn Errors of Immunity. Cells were sorted prior to sequencing based on proliferation (dilution of Cell Trace Violet) or activation (expression of CD69 and/or CD25).

  单细胞
• Species-Dependent WNT/ß-Catenin Signaling Orchestrates Epiblast Morphogenesis during Early Implantation [RNA-Seq]
  GSE273623Homo sapiens15 个样本2026-10-30

  The precise orchestration of epiblast tissue remodeling during implantation is critical for mammalian embryonic development and the regulatory link between cellular signaling and epiblast tissue morphogenesis remains unexplored. We present a fully defined, 3D epiblast-like model derived from human pluripotent stem cells (hPSCs). Functional studies of these in vitro models, alongside in vivo investigations in human and mouse embryos, reveal the pivotal role of canonical WNT signaling in mammalian epiblast morphogenesis. In humans, WNT/β-catenin signaling is crucial for epithelization, rosette formation, and cavitation of epiblast tissue. In mice, inhibition of canonical WNT signaling supports these events. Dual CUT&RUN and RNA sequencing, complemented by multi-study comparative transcriptome profiling, identify a TCF/LEF-mediated mechanism linking WNT signaling to lipid metabolism in human epiblast morphogenesis. This study highlights divergent roles of WNT-mediated mechanisms in early mouse and human development, as well as potential causes of human embryo lethality at implantation.
• Exploration of microRNAs involved in cervical lymph node metastasis of oral squamous cell carcinoma
  GSE246620Homo sapiens12 个样本2026-10-30

  Exploring biomarkers involved in lymph node metastasis in oral cancer
• Epigenomic analysis of the myometrium during late implantation revealed regulatory elements in genes related to the cellular zinc homeostasis pathway in pigs
  GSE246434Sus scrofa24 个样本2026-10-30

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Epigenomic analysis of the myometrium during late implantation revealed regulatory elements in genes related to the cellular zinc homeostasis pathway in pigs (ChIP-Seq)
  GSE246433Sus scrofa12 个样本2026-10-30

  The myometrium, composed of the inner circular muscle (CM) and outer longitudinal muscle (LM), is crucial in establishing and maintaining early pregnancy. However, the molecular mechanisms involved are not well understood. In this study, we identified the transcriptomic features of the CM and LM collected from the mesometrial (M) and anti-mesometrial (AM) sides of the pig uterus on day 18 of pregnancy during the placentation initiation phase. Some genes in the cellular zinc ion level regulatory pathways (MT-1A, MT-1D, MT-2B, SLC30A2, and SLC39A2) were spatially and highly enriched in uterine CM at the mesometrial side. In addition, the histone modification profiles of H3K27ac and H3K4me3 in uterine CM and LM collected from the mesometrial side were characterized. Genomic regions associated with the expression of genes regulating the cellular zinc ion level were detected. Moreover, six highly linked variants in the H3K27ac-enriched region of the pig SLC30A2 gene were identified and found to be significantly associated with the total number born at the second parity (P < 0.05). In conclusion, the genes in the pathways of cellular zinc homeostasis and their regulatory elements identified have implications for pig reproduction trait improvement and warrant further investigations.

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