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 [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.
• Transcriptomic profiling of primary rat nucleus pulposus cells cultured in soft and stiff GelMA hydrogels
  GSE344937Rattus norvegicus6 个样本2026-10-30

  This study profiles gene expression in primary rat nucleus pulposus cells encapsulated in 10% GelMA hydrogels with either 30% or 60% methacryloyl substitution. Three independent biological replicates were sequenced for each matrix condition.
• Time series analysis of transcriptomic responses to iron and zinc stress in Poplar
  GSE344088Populus trichocarpa173 个样本2026-10-30

  Extending our understanding of iron (Fe) and zinc (Zn) homeostasis beyond annual model plants is essential for improving plant productivity, nutritional quality, and food safety. However, the mechanisms coordinating metal acquisition, systemic signaling, and detoxification remain poorly understood in woody perennials. We generated a 21-d time-series multi-omics resource integrating transcriptomic, ionomic, and physiological measurements from roots and leaves of black cottonwood (Populus trichocarpa) exposed to Fe or Zn deficiency or excess. Temporal analyses revealed tissue-specific metal partitioning, extensive nutrient crosstalk, and restriction of Zn accumulation during prolonged Zn excess. Gene regulatory network inference identified bHLH38/39.2 as a hub associated with root Fe uptake and leaf Fe signaling. Fe deficiency rapidly induced five C-TERMINALLY ENCODED PEPTIDE (CEP) genes in roots. A fluorescently labeled CEP peptide supplied to roots accumulated in leaves, where CEP treatment induced IRON MAN (IMA) genes. Receptor-dependent protoplast assays further demonstrated CEP-mediated activation of IMA promoters. These findings support a model in which root-derived CEP peptides convey Fe status to leaf IMA signaling. Under Zn excess, declining Zn accumulation coincided with increased root suberization and induction of suberin-biosynthetic genes. NAC058.1 and NAC058.2 emerged as regulatory hubs and activated most tested suberin gene promoters. These findings suggest that NAC-regulated suberization restricts Zn entry during prolonged exposure. Our study identifies systemic and barrier-based mechanisms of micronutrient homeostasis in a woody perennial.

  多组学
• 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.
• Mycobacterium abscessus inhibits IFNg activation, impairing control of intracellular infection
  GSE339253Homo sapiens80 个样本2026-10-30

  Mycobacterium abscessus (Mab) is an emerging pathogen among the nontuberculous mycobacteria (NTM), causing infections in individuals with lung conditions (e.g. cystic fibrosis) or immunodeficiency (e.g. impaired interferon gamma (IFNg) production or response pathway). Mab infections are difficult to treat, and adjunctive therapy with IFNg is sometimes used for refractory infections. However, the reasons that endogenous IFNg fails to control infections remain unknown. Using a THP-1 macrophage-mycobacteria infection model, we studied the combined effects of IFNg and imipenem (IPM) on intracellular M. abscessus. Through flow cytometry, RNAseq and cytokine measurements in infected cells treated for over 24 hours with IPM and IFNg alone or in combination, we identified distinct cellular response pathways at different stages of infection. In early stages of infection, IFNg pathway signaling, as assessed by STAT1 phosphorylation level, was preserved, while there were changes in TNFa, IL1b and IL6 inflammatory pathways in response to the infection. However, after 24 hrs of infection the IFNg signaling was impaired. Addition of imipenem abolished the impairment in IFNg signaling and led to a significant decrease in intracellular bacterial load. At 48 hrs, treatment with IFNg alone or combined with IPM significantly reduced the IFNg receptor1 surface display, while total cellular IFNgR1 and IFNgR2 levels remained unchanged. Mycobacterium abscessus reduces STAT1 phosphorylation and blunts IFNg signaling, thereby limiting macrophage activation and facilitating intracellular mycobacterial growth. Imipenem counteracts this suppression, reactivates antimicrobial pathways, enhances IFNg-mediated killing, and promotes bacterial clearance. Understanding M. abscessus immune subversion and how to counter it is crucial for developing effective antimicrobial therapies.
• RNA-bound MYBL2 engages the oncogenic transcription factors MAFG and FRA1 to promote melanoma
  GSE335104Homo sapiens9 个样本2026-10-30

  Non-mutational mechanisms, including copy number alterations and transcription factor dysregulation, are critical drivers of melanoma progression. We identify the transcription factor MYBL2 as a key oncogenic driver located on frequently amplified chromosome 20q. MYBL2 overexpression promotes transformation and correlates with poor survival, yet paradoxically, its transactivation function is dispensable for oncogenic activity. Instead, MYBL2 acquires a previously unrecognized non-canonical RNA binding function in melanoma cells enabled by the melanoma-associated RNA landscape. Through these RNA interactions, MYBL2 reshapes the chromatin landscape toward an AP-1 permissive state and promotes chromatin association of the oncogenic transcription factors MAFG and FRA1, indirectly reprogramming tumor-promoting gene networks whose expression predicts poor outcomes across multiple cancers. Importantly, disrupting the MYBL2-RNA interaction using a small decoy RNA impairs MYBL2 association with MAFG and FRA1 and suppresses melanoma cell growth. Our findings establish MYBL2 as an RNA binding-dependent, 20q gain-associated driver of melanoma and reveal that MYBL2-RNA interactions promote melanoma progression through chromatin and transcriptional network remodeling.
• 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.
• Diagnostic value of a panel of serum exosomal miRNAs as potential biomarkers for pancreatic cancer
  GSE332591Homo sapiens96 个样本2026-10-30

  Exosomes and exosomal miRNAs were isolated from the serum of patients with pancreatic cancer, cholangiocarcinoma, duodenal cancer, pancreatic benign tumor and healthy individuals. Exosomal miRNAs were analyzed using next-generation sequencing (NGS) to identify miRNA candidates for diagnosis.
• RNAseq data from canine normal brain tissue
  GSE330017Canis lupus familiaris7 个样本2026-10-30

  Canine normal brain tissue samples in this dataset were utilized for comparative genomics analyses for a previously published dataset of canine gliomablastoma. These data were used to provide the first comprehensive cross-species comparison of the three canonical glioblastoma pathways – RTK/RAS/PI(3)K, p53 and Rb – across adult human, pediatric human and canine glioma, alongside in-depth characterization of the tumor microenvironment (TME).
• 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.
• Detection of a sequence feature for recursive splicing
  GSE327295Homo sapiens5 个样本2026-10-30

  RNA splicing is directed by cis-acting sequence signals interacting with trans-acting factors to remove introns from newly transcribed pre-mRNA, joining exons to generate mature mRNA. Splicing happens far more often than observed exon-exon junctions in mRNA. As one contributing process, the spliceosome progressively removes large introns in small segments by ‘recursive splicing’, instead of splicing the whole intron at one time. However, the cis-acting sequences associated with recursive splicing have not been identified. Using probabilistic mixture models, we found that recursive splicing occurs more frequently in first introns, which are typically longer, and exhibit a distinct CG-rich sequence feature in the sequences flanking the upstream 5’SS, and depletion of CGs in the downstream polypyrimidine tract. Remarkably, recursive splicing is also more frequent in downstream introns of genes containing first introns with these properties. Mechanistically, these data suggest that early events in RNA synthesis and processing influence the prevalence of recursive splicing for the rest of the transcript. Finally, we developed a sequence-dependent classifier for recursive splicing, which we tested with a novel medium-throughput primer extension assay. In summary, the usage of recursive splicing sites is established at the beginning of RNA synthesis through newly-identified sequence motifs flanking both ends of the first intron.

  计算与 AI
• Aberrant stabilization of the m6A reader IGF2BP3 drives metastatic progression and 5-FU refractoriness in FBXW7-mutant colorectal cancer
  GSE326794Homo sapiens4 个样本2026-10-30

  Loss of the E3 ubiquitin ligase FBXW7 leads to aberrant stabilization of the m6A reader IGF2BP3 in colorectal cancer. To identify the RNA targets of IGF2BP3 under FBXW7-deficient conditions, we performed HITS-CLIP-seq in isogenic DLD1 FBXW7 wild-type and knockout cell lines. CLIP-seq analysis revealed that IGF2BP3-binding sites were enriched in 3' UTR regions of protein-coding mRNAs, and that IGF2BP3 preferentially bound cancer-promoting transcripts including DPYD and COL4A1.
• 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.
• Establishment of a multi-stage in vitro screening platform to identify candidate compounds for intestinal mucosal damage in inflammatory bowel disease
  GSE321659Homo sapiens9 个样本2026-10-30

  Mucosal healing is a key therapeutic goal in inflammatory bowel disease (IBD), which is characterized by mucosal lesions in the gastrointestinal tract. For IBD drug development, it is important to identify multiple compounds with strong effects on mucosal injury and different mechanisms of action. Here, we established an intestinal organoid-based assay to evaluate cytokine-induced inflammatory and epithelial stress responses. We also developed an intestinal microphysiological system (intestinal MPS)-based assay for quantitative evaluation of cytokine-induced changes in mucosal architecture. By integrating these assays, we constructed a multi-stage screening platform to identify candidate compounds that suppress inflammatory responses and preserve mucosal architecture. Tofacitinib, an approved IBD drug, showed positive effects in these assays, supporting the relevance of this platform. Although organoid-based screening identified pimitespib as a candidate compound, pimitespib did not improve mucosal architecture in the intestinal MPS. Consistently, pimitespib failed to restore mucosal morphology in an IBD mouse model. These findings suggest that combining intestinal organoids with an intestinal MPS may help identify candidate compounds that suppress inflammatory responses while preserving mucosal architecture.
• 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.