학술논문
Intrinsic epigenetic control of angiogenesis in induced pluripotent stem cell-derived endothelium regulates vascular regeneration.
Document Type
Academic Journal
Author
Macklin BL; Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology, Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD, 21218, USA.; Lin YY; Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology, Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD, 21218, USA.; Emmerich K; Department of Ophthalmology, Wilmer Eye Institute and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.; Wisniewski E; Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology, Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD, 21218, USA.; Polster BM; Department of Anesthesiology and Center for Shock, Trauma, and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.; Konstantopoulos K; Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology, Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD, 21218, USA.; Mumm JS; Department of Ophthalmology, Wilmer Eye Institute and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.; Gerecht S; Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology, Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD, 21218, USA. sharon.gerecht@duke.edu.; Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA. sharon.gerecht@duke.edu.
Source
Publisher: Nature Publishing Group, published in partnership with Monash University and Australian Regenerative Medicine Institute Country of Publication: United States NLM ID: 101699846 Publication Model: Electronic Cited Medium: Internet ISSN: 2057-3995 (Electronic) Linking ISSN: 20573995 NLM ISO Abbreviation: NPJ Regen Med Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
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.
(© 2022. The Author(s).)
(© 2022. The Author(s).)