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Epigenetic Activation of Pro-angiogenic Signaling Pathways in Human Endothelial Progenitors Increases Vasculogenesis. | LitMetric

Epigenetic Activation of Pro-angiogenic Signaling Pathways in Human Endothelial Progenitors Increases Vasculogenesis.

Stem Cell Reports

Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, General Hospital, Mailbox 511, 501 Smyth Road, Ottawa, ON K1H8L6, Canada; University of Ottawa, Department of Cellular and Molecular Medicine, Ottawa, ON K1H8L6, Canada; Ottawa Institute of Systems Biology, Ottawa, ON K1H8M5, Canada. Electronic address:

Published: November 2017

AI Article Synopsis

Article Abstract

Human endothelial colony-forming cells (ECFCs) represent a promising source of adult stem cells for vascular repair, yet their regenerative capacity is limited. Here, we set out to understand the molecular mechanism restricting the repair function of ECFCs. We found that key pro-angiogenic pathways are repressed in ECFCs due to the presence of bivalent (H3K27me3/H3K4me3) epigenetic marks, which decreases the cells' regenerative potential. Importantly, ex vivo treatment with a combination of epigenetic drugs that resolves bivalent marks toward the transcriptionally active H3K4me3 state leads to the simultaneous activation of multiple pro-angiogenic signaling pathways (VEGFR, CXCR4, WNT, NOTCH, SHH). This in turn results in improved capacity of ECFCs to form capillary-like networks in vitro and in vivo. Furthermore, restoration of perfusion is accelerated upon transplantation of drug-treated ECFCs in a model of hindlimb ischemia. Thus, ex vivo treatment with epigenetic drugs increases the vascular repair properties of ECFCs through transient activation of pro-angiogenic signaling pathways.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830028PMC
http://dx.doi.org/10.1016/j.stemcr.2017.09.009DOI Listing

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