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Bulk RNA-seq datasets supporting analysis of the MYC–USP10–SOX4 pathway in thymocytes and T-ALL

ABSTRACT: This study presents bulk RNA-seq datasets generated from thymocytes of C57BL/6J mice to elucidate the transcriptional impact of thymus-specific loss of the deubiquitinase USP10. Total RNA was isolated from age-matched wild-type (WT) and USP10 conditional-knockout (USP10-cKO) thymus tissues, poly(A)+ fractions were enriched, and paired-end 150 bp libraries were sequenced on an Illumina NovaSeq 6000 platform. The resulting expression profiles allow direct comparison of global gene-expression programs between normal thymocyte development and USP10-deficient conditions, providing a resource for identifying USP10-regulated pathways, discerning stage-specific transcriptional alterations, and advancing our understanding of how ubiquitin signaling modulates early T-cell differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE300637 | GEO | 2026/02/13

REPOSITORIES: GEO

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Project description:Aims: Cardiac fibroblasts (CFs) play a crucial role in cardiac remodelling, which is a common cause of heart failure (HF). However, the molecular mechanisms underlying the fibroblast-to-myofibroblast transition remain largely unknown. Foxm1 is well known in various cardiopulmonary pathologies. However, Foxm1-driven CF activation in the progression of cardiac remodelling to HF remains to be investigated. Methods: Changes in Foxm1 expression were assessed in samples from patients with HF and mice with transverse aortic constriction (TAC)-induced cardiac remodelling. Pharmacologic antagonist FDI-6 was used to explore the effects of Foxm1 inhibition on post-TAC outcomes. Tcf21-Cre and PostnMCM were used to evaluate Foxm1 loss- and gain-of-function in CFs and myofibroblasts, respectively. Cardiac function and remodelling were examined by echocardiography and histological analysis. Foxm1 downstream target genes were identified by mass spectrometry (MS) and transcriptomic analysis. Post-translational regulation was evaluated by in vitro chromatin immunoprecipitation, co-immunoprecipitation, and ubiquitination assays. Pharmacological inhibition of Usp10 or knockout of p38γ in vivo verified the signalling pathway by which Foxm1 regulated cardiac remodelling. Results: Foxm1 was upregulated in human HF samples as well as in the mouse cardiac remodelling model. CFs were the primary cell type responsible for Foxm1 upregulation. Foxm1 pharmacological inhibition or genetic knockout in CFs or myofibroblasts significantly attenuated TAC-induced cardiac remodelling and HF. Conversely, conditional overexpression of Foxm1 in CFs or myofibroblasts resulted in more severe pathological cardiac remodelling and dysfunction. Combined RNA-sequencing and MS analysis revealed that Foxm1 promoted Usp10 expression by binding to its promoter. Usp10 interacted with p38γ, resulting in p38γ deubiquitination and thus inﬂuencing the downstream p38 mitogen-activated protein kinase (MAPK) signalling pathway. Pharmacological inhibition of Usp10 or genetic knockout of p38γ ameliorated the exacerbated TAC-induced cardiac remodelling in mice with myofibroblast-specific Foxm1 overexpression. Conclusion: Our findings reveal an essential role of Foxm1 in CF activation during cardiac remodelling. These results suggest that targeting the Foxm1/Usp10/p38γ MAPK axis may represent a new potential therapeutic strategy against pathological cardiac remodelling and HF.

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Bulk RNA-seq datasets supporting analysis of the MYC–USP10–SOX4 pathway in thymocytes and T-ALL

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