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Intrinsic epigenetic control of angiogenesis in induced pluripotent stem cell-derived endothelium regulates vascular regeneration.

Publication ,  Journal Article
Macklin, BL; Lin, Y-Y; Emmerich, K; Wisniewski, E; Polster, BM; Konstantopoulos, K; Mumm, JS; Gerecht, S
Published in: NPJ Regenerative medicine
May 2022

Human-induced pluripotent stem cell-derived endothelial cells (iECs) provide opportunities to study vascular development and regeneration, develop cardiovascular therapeutics, and engineer model systems for drug screening. The differentiation and characterization of iECs are well established; however, the mechanisms governing their angiogenic phenotype remain unknown. Here, we aimed to determine the angiogenic phenotype of iECs and the regulatory mechanism controlling their regenerative capacity. In a comparative study with HUVECs, we show that iECs increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) mediates their highly angiogenic phenotype via regulation of glycolysis enzymes, filopodia formation, VEGF mediated migration, and robust sprouting. We find that the elevated expression of VEGFR2 is epigenetically regulated via intrinsic acetylation of histone 3 at lysine 27 by histone acetyltransferase P300. Utilizing a zebrafish xenograft model, we demonstrate that the ability of iECs to promote the regeneration of the amputated fin can be modulated by P300 activity. These findings demonstrate how the innate epigenetic status of iECs regulates their phenotype with implications for their therapeutic potential.

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Published In

NPJ Regenerative medicine

DOI

EISSN

2057-3995

ISSN

2057-3995

Publication Date

May 2022

Volume

7

Issue

1

Start / End Page

28

Related Subject Headings

  • 3208 Medical physiology
  • 3206 Medical biotechnology
 

Citation

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Macklin, B. L., Lin, Y.-Y., Emmerich, K., Wisniewski, E., Polster, B. M., Konstantopoulos, K., … Gerecht, S. (2022). Intrinsic epigenetic control of angiogenesis in induced pluripotent stem cell-derived endothelium regulates vascular regeneration. NPJ Regenerative Medicine, 7(1), 28. https://doi.org/10.1038/s41536-022-00223-w
Macklin, Bria L., Ying-Yu Lin, Kevin Emmerich, Emily Wisniewski, Brian M. Polster, Konstantinos Konstantopoulos, Jeff S. Mumm, and Sharon Gerecht. “Intrinsic epigenetic control of angiogenesis in induced pluripotent stem cell-derived endothelium regulates vascular regeneration.NPJ Regenerative Medicine 7, no. 1 (May 2022): 28. https://doi.org/10.1038/s41536-022-00223-w.
Macklin BL, Lin Y-Y, Emmerich K, Wisniewski E, Polster BM, Konstantopoulos K, et al. Intrinsic epigenetic control of angiogenesis in induced pluripotent stem cell-derived endothelium regulates vascular regeneration. NPJ Regenerative medicine. 2022 May;7(1):28.
Macklin, Bria L., et al. “Intrinsic epigenetic control of angiogenesis in induced pluripotent stem cell-derived endothelium regulates vascular regeneration.NPJ Regenerative Medicine, vol. 7, no. 1, May 2022, p. 28. Epmc, doi:10.1038/s41536-022-00223-w.
Macklin BL, Lin Y-Y, Emmerich K, Wisniewski E, Polster BM, Konstantopoulos K, Mumm JS, Gerecht S. Intrinsic epigenetic control of angiogenesis in induced pluripotent stem cell-derived endothelium regulates vascular regeneration. NPJ Regenerative medicine. 2022 May;7(1):28.

Published In

NPJ Regenerative medicine

DOI

EISSN

2057-3995

ISSN

2057-3995

Publication Date

May 2022

Volume

7

Issue

1

Start / End Page

28

Related Subject Headings

  • 3208 Medical physiology
  • 3206 Medical biotechnology