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dc.contributor.authorMacklin, Bria L
dc.contributor.authorLin, Ying-Yu
dc.contributor.authorEmmerich, Kevin
dc.contributor.authorWisniewski, Emily
dc.contributor.authorPolster, Brian M
dc.contributor.authorKonstantopoulos, Konstantinos
dc.contributor.authorMumm, Jeff S
dc.contributor.authorGerecht, Sharon
dc.date.accessioned2022-05-17T13:18:34Z
dc.date.available2022-05-17T13:18:34Z
dc.date.issued2022-05-12
dc.identifier.urihttp://hdl.handle.net/10713/18874
dc.description.abstractHuman-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.en_US
dc.description.urihttps://doi.org/10.1038/s41536-022-00223-wen_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofNPJ Regenerative Medicineen_US
dc.rights© 2022. The Author(s).en_US
dc.titleIntrinsic epigenetic control of angiogenesis in induced pluripotent stem cell-derived endothelium regulates vascular regeneration.en_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41536-022-00223-w
dc.identifier.pmid35551465
dc.source.journaltitleNPJ Regenerative medicine
dc.source.volume7
dc.source.issue1
dc.source.beginpage28
dc.source.endpage
dc.source.countryUnited States


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