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Heterochromatin Protein 1 Alpha (HP1α: CBX5) is a Key Regulator in Differentiation of Endothelial Progenitor Cells to Endothelial Cells

 Yong-Sun Maeng  ;  Ja Young Kwon  ;  Eung Kweon Kim  ;  Young-Guen Kwon 
 STEM CELLS, Vol.33(5) : 1512-1522, 2015 
Journal Title
Issue Date
Animals ; Blood Vessels/growth & development ; Cell Differentiation* ; Cell Movement ; Chromosomal Proteins, Non-Histone/metabolism* ; Endothelial Progenitor Cells/cytology* ; Endothelial Progenitor Cells/metabolism* ; Epigenesis, Genetic ; Gene Expression Regulation ; Gene Knockdown Techniques ; Humans ; In Vitro Techniques ; Male ; Mice, Inbred C57BL ; Neovascularization, Physiologic ; Wound Healing
Differentiation ; Epigenetics ; HP1α ; Neovascularization
As the ability to control the differentiation of endothelial stem/progenitor cells (EPCs) into vascular endothelial cell lineages could be useful for promoting neovascularization, it is important to obtain a deeper understanding of the epigenetic mechanisms that regulate EPC differentiation and neovascularization. Heterochromatin protein 1α (HP1α) is known to be involved in the epigenetic regulation of gene silencing. However, recent reports demonstrate that HP1α can also activate gene expression during cell differentiation. In this study, microarray analysis revealed that HP1α expression was induced during EPC differentiation and is associated with the expression of outgrowing endothelial cell (OEC)-specific protein markers. To explore the role of HP1α in the differentiation of EPCs to OECs, its expression was knocked-down or over-expressed in differentiating EPCs. Overexpression of HP1α promoted the differentiation and angiogenic activity of EPCs in vitro and in vivo, whereas knockdown of HP1α led to a defect in OEC migration, tube formation, and angiogenic sprouting activity. Gene expression profiling showed increased expression of angiogenic genes, including NOTCH1, cadherin-5, and angiopoietin-like-2, and decreased expression of progenitor cell marker genes, including CD133, CXCR4, and C-KIT, in HP1α-overexpressing EPCs. Also, increased HP1α at an early stage of EPC differentiation may regulate angiogenic gene transcription by interacting with chromatin that modifies epigenetic factors such as the methyl-CpG binding domain, Polycomb group ring finger 2, and DNA methyltransferases. Our findings demonstrate, for the first time, that HP1α plays an important role in the differentiation and angiogenic function of EPCs by regulating endothelial gene expression. Stem Cells 2015;33:1512-1522.
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Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Ja Young(권자영) ORCID logo https://orcid.org/0000-0003-3009-6325
Kim, Eung Kweon(김응권) ORCID logo https://orcid.org/0000-0002-1453-8042
Maeng, Yong Sun(맹용선) ORCID logo https://orcid.org/0000-0003-1694-8405
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