Sox17 and Erg synergistically activate endothelial cell fate in reprogramming fibroblasts.

Autor: Farber G; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Takasugi P; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Ricketts S; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Wang H; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Xie Y; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Farber E; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Liu J; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Qian L; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: li_qian@med.unc.edu.
Jazyk: angličtina
Zdroj: Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2024 Dec 16; Vol. 199, pp. 33-45. Date of Electronic Publication: 2024 Dec 16.
DOI: 10.1016/j.yjmcc.2024.11.012
Abstrakt: Sox17-Erg direct reprogramming is a potent tool for the in vitro and in vivo generation of arterial-like induced-endothelial cells from fibroblasts. In this study, we illustrate the pioneering roles of both Sox17 and Erg in the endothelial cell reprogramming process and demonstrate that emergent gene expression only occurs when both factors are co-expressed. Bioinformatic analyses and molecular validation reveal both Bach2 and Etv4 as integral mediators of Sox17-Erg reprogramming with different roles in lung and heart fibroblast reprogramming. The generated organ-specific induced endothelial cells express molecular signatures similar to vasculature found in the starting cell's organ of origin and the starting chromatin architecture plays a role in the acquisition of this organ-specific identity. Overall, the Sox17-Erg reprogramming mechanism provides foundational knowledge for the future recapitulation of vascular heterogeneity through direct reprogramming.
Competing Interests: Declaration of competing interest None.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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