1. Stem Cell Reports Ar ticle Epigenetic Activation of Pro-angiogenic Signaling Pathways in Human Endothelial Progenitors Increases Vasculogenesis
- Author
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Fraineau, Sylvain, Palii, Carmen, McNeill, Brian, Ritso, Morten, Shelley, William, Prasain, Nutan, Chu, Alphonse, Vion, Elodie, Rieck, Kristy, Nilufar, Sharmin, Perkins, Theodore, Rudnicki, Michael, Allan, David, Yoder, Mervin, Suuronen, Erik, Brand, Marjorie, Ottawa Hospital Research Institute [Ottawa] (OHRI), University of Ottawa [Ottawa], University of Ottawa Heart Institute, Indiana University School of Medicine, Indiana University System, and Fraineau, Sylvain
- Subjects
[SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,[SDV]Life Sciences [q-bio] ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,[SDV] Life Sciences [q-bio] ,[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences ,[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology - Abstract
International audience; 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.
- Published
- 2017