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

Gregory Farber, Yanhan Dong, Qiaozi Wang, Mitesh Rathod, Haofei Wang, Michelle Dixit, Benjamin Keepers, Yifang Xie, Kendall Butz, William J. Polacheck, Jiandong Liu and Li Qian ()
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Gregory Farber: The University of North Carolina at Chapel Hill
Yanhan Dong: The University of North Carolina at Chapel Hill
Qiaozi Wang: The University of North Carolina at Chapel Hill
Mitesh Rathod: University of North Carolina at Chapel Hill and North Carolina State University
Haofei Wang: The University of North Carolina at Chapel Hill
Michelle Dixit: The University of North Carolina at Chapel Hill
Benjamin Keepers: The University of North Carolina at Chapel Hill
Yifang Xie: The University of North Carolina at Chapel Hill
Kendall Butz: The University of North Carolina at Chapel Hill
William J. Polacheck: The University of North Carolina at Chapel Hill
Jiandong Liu: The University of North Carolina at Chapel Hill
Li Qian: The University of North Carolina at Chapel Hill

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-48354-6

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