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

Author

Listed:
  • 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
    University of North Carolina Kidney Center)

  • 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
    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
    University of North Carolina at Chapel Hill and North Carolina State University)

  • Jiandong Liu

    (The University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill)

  • Li Qian

    (The University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill)

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.

Suggested Citation

  • Gregory Farber & Yanhan Dong & Qiaozi Wang & Mitesh Rathod & Haofei Wang & Michelle Dixit & Benjamin Keepers & Yifang Xie & Kendall Butz & William J. Polacheck & Jiandong Liu & Li Qian, 2024. "Direct conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48354-6
    DOI: 10.1038/s41467-024-48354-6
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