Identification of Epigenetic Regulators of Fibrotic Transformation in Cardiac Fibroblasts Through Bulk and Single-Cell CRISPR Screens

• DOI: 10.32388/2cc4zm
• Publication Date: 2025-04-23T16:40:15Z
• Authors: Laura Pilar Aguad...; Nerea Garitano; Wolfgang Esser-Skala; Judy Sayers; Cynthia del Valle; Daniel Alameda-Se...; Julen Mendieta-Es...; Maria Erendira Ca...; Ainhoa Goñi-Salav...; Jon Zazpe; Anna Rosaria de Vito; Francesco Marchese; Diego Alignani; Juliana Cudini; Torsten Gross; Gregorio Rábago; Nisha Narayan; Laura Martinez; Sonia Martinez; Brian Huntly; Paul Riley; Arantxa Gonzalez-...; Jake P. Taylor-King; Nikolaus Fortelny; Beatriz Pelacho; David Lara-Astiaso
• Keywords: Identification; Single-Cell Analysis

Cardiac fibrosis is mediated by the persistent activity of myofibroblasts, which differentiate from resident cardiac fibroblasts in response to tissue damage and stress signals. The signaling pathways transcription factors regulating fibrotic transformation have been thoroughly studied. In contrast, roles chromatin myofibroblast differentiation their contribution pathogenic remain poorly understood. Here, we combined bulk single-cell CRISPR screens characterize primary fibroblasts. We uncover strong regulators states including Srcap Kat5 remodelers. confirm that these are required for functional processes underlying collagen synthesis cell contractility. Using profiling perturbed fibroblasts, demonstrate pro-fibrotic complexes facilitate well-characterized factors. Finally, show KAT5 inhibition alleviates responses patient-derived human