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Single-nucleus RNA sequencing combined with fluorescence in situ hybridization reveals Stat3 as a therapeutic target for ventilator-induced diaphragm dysfunction

ABSTRACT: snRNA-seq revealed that MV induced significant changes in the cellular composition and transcriptional profiles of diaphragm tissue. Specifically, fibroblasts and type IIb myofibers showed increased proportions, while type IIx myofibers and other cell types, such as fibro/adipogenic progenitors (FAPs), showed a decrease in their representation. Transcriptionally, MV led to the upregulation of key muscle atrophy-related genes such as Atrogin-1 and Murf-1, as well as fibrosis-related genes including collagen and fibronectin. Stat3 emerged as a central player, with its expression significantly elevated in both myofibers and fibroblasts. Further analysis of gene regulatory networks demonstrated that Stat3 activation was associated with disrupted muscle metabolism, increased fibroblast activity, and enhanced fibrotic signaling pathways. FISH confirmed the spatial localization of these transcriptional changes, corroborating the snRNA-seq findings. The increased activity of Stat3, particularly in promoting fibrosis and muscle degradation, suggests that it is a key regulator in the pathogenesis of VIDD.

ORGANISM(S): Mus musculus

PROVIDER: GSE276162 | GEO | 2025/09/01

REPOSITORIES: GEO

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