title: Enhancement of differentiation efficiency of hESCs into vascular lineage cells in hypoxia via a paracrine mechanism.
abstract: Hypoxia is one way of inducing differentiation due to the activation of the key regulatory factor, Hypoxia-inducible factor 1 alpha (HIF-1α). However, the action of HIF-1α on the differentiation of hESCs was unclear until now. To investigate the effect of hypoxia on the differentiation of hESCs, we compared the differentiation efficacy into vascular lineage cells under normoxic and hypoxic conditions. We observed HIF-1α expression and the related expression of pro-angiogenic factors VEGF, bFGF, Ang-1 and PDGF in hEBs cultured under hypoxic conditions. Along with this, differentiation efficacy into vascular lineage cells was improved under hypoxic conditions. When HIF-1α was blocked by echinomycin, both angiogenic factors and the differentiation efficacy were down-regulated, suggesting that the enhancement of differentiation efficacy was caused by intrinsic up-regulation of HIF-1α and these pro-angiogenic factors under hypoxic condition. This response might be primarily regulated by the HIF-1α signal pathway, and hypoxia might be the key to improving the differentiation of hESCs into vascular lineage cells. Therefore, this study demonstrated that microenvironmental changes (i.e., hypoxia) can improve differentiation efficacy of hESCs into a vascular lineage without exogenous factors via cell-intrinsic up-regulation of angiogenic factors. These facts will contribute to the regulation of stem cell fate.
authors: CHA Bio & Diostech Co., Ltd. 606-16 Yeoksam 1 dong, Gangnam gu, Seoul 135-907, Republic of Korea.
authors: Jeong Min
authors: JM
authors: Shin
authors: Jumi
authors: J
authors: Kim
authors: Hye Eun
authors: HE
authors: Kim
authors: Min Ji
authors: MJ
authors: Lee
authors: Kyung Il
authors: KI
authors: Lee
authors: Eun Gyong
authors: EG
authors: Yoo
authors: Young Joo
authors: YJ
authors: Jeon
authors: Dong-Wook
authors: DW
authors: Kim
authors: Jung-Il
authors: JI
authors: Chae
authors: Hyung Min
authors: HM
authors: Chung
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D004448:Echinomycin / Q000494:pharmacology; D058732:Embryoid Bodies / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019899:Paracrine Communication / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D043925:Angiogenesis Inducing Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D004448:Echinomycin