HDAC3是剪切力和VEGF诱导胚胎干细胞向内皮细胞方向分化的关键因子
生物谷报道：我们已经知道剪切力或者VEGF均可以诱导胚胎干细胞向内皮细胞方向分化，但是是如何通路发挥作用呢？已知某些信号分子在其中起到一定的作用。华人学者许清波最新研究发现：Flk-1–PI3K–Akt–HDAC3–p53–p21通路在其中扮演着核心作用。这一通路完整地揭示了胚胎干细胞向内皮细胞方向分化的共同通路，为定向控制胚胎干细胞分化提供重要理论基础。
原始出处：
HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells
J. Cell Biol. 2006 174: 1059-1069. Published Sep 18 2006, 10.1083/jcb.200605113.
英文摘要：
Reendothelialization involves endothelial progenitor cell (EPC) homing, proliferation, and differentiation, which may be influenced by fluid shear stress and local flow pattern. This study aims to elucidate the role of laminar flow on embryonic stem (ES) cell differentiation and the underlying mechanism. We demonstrated that laminar flow enhanced ES cell–derived progenitor cell proliferation and differentiation into endothelial cells (ECs). Laminar flow stabilized and activated histone deacetylase 3 (HDAC3) through the Flk-1–PI3K–Akt pathway, which in turn deacetylated p53, leading to p21 activation. A similar signal pathway was detected in vascular endothelial growth factor–induced EC differentiation. HDAC3 and p21 were detected in blood vessels during embryogenesis. Local transfer of ES cell–derived EPC incorporated into injured femoral artery and reduced neointima formation in a mouse model. These data suggest that shear stress is a key regulator for stem cell differentiation into EC, especially in EPC differentiation, which can be used for vascular repair, and that the Flk-1–PI3K–Akt–HDAC3–p53–p21 pathway is crucial in such a process.
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