Direct conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg.

Autor: Farber G; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Dong Y; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Wang Q; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Rathod M; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill and Raleigh, NC, USA.; University of North Carolina Kidney Center, Chapel Hill, NC, USA., Wang H; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Dixit M; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Keepers B; 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., Xie Y; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Butz K; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Polacheck WJ; The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill and Raleigh, NC, 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. li_qian@med.unc.edu.; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. li_qian@med.unc.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 16; Vol. 15 (1), pp. 4170. Date of Electronic Publication: 2024 May 16.
DOI: 10.1038/s41467-024-48354-6
Abstrakt: Endothelial cells are a heterogeneous population with various organ-specific and conserved functions that are critical to organ development, function, and regeneration. Here we report a Sox17-Erg direct reprogramming approach that uses cardiac fibroblasts to create differentiated endothelial cells that demonstrate endothelial-like molecular and physiological functions in vitro and in vivo. Injection of these induced endothelial cells into myocardial infarct sites after injury results in improved vascular perfusion of the scar region. Furthermore, we use genomic analyses to illustrate that Sox17-Erg reprogramming instructs cardiac fibroblasts toward an arterial-like identity. This results in a more efficient direct conversion of fibroblasts into endothelial-like cells when compared to traditional Etv2-based reprogramming. Overall, this Sox17-Erg direct reprogramming strategy offers a robust tool to generate endothelial cells both in vitro and in vivo, and has the potential to be used in repairing injured tissue.
(© 2024. The Author(s).)
Databáze: MEDLINE
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