Huan Qing, Wang Yan, Yang Lixia, Cui Yuqian, Wen Ji, Chen Jun, Chen Zi-Jiang
1 Reproductive Medical Center, the Second Hospital affiliated to Shandong University of Traditional Chinese Medicine , Jinan, 250001, People's Republic of China .
Cell Reprogram. 2015 Feb;17(1):59-68. doi: 10.1089/cell.2014.0020. Epub 2014 Dec 30.
ID1 can mediate transforming growth factor-β (TGF-β)/activin receptor-like kinase-1 (ALK1)-induced (and Smad-dependent) migration in endothelial cells (ECs). However, the role that ID1 plays during differentiation of human embryonic stem cells (hESCs) into ECs induced by TGF-β1 remains unclear. In this study, a hESC differentiation model that recapitulates the developmental steps of vasculogenesis during the early stages of embryonic development was used to explore this question. We found that TGF-β1 increases endothelial cell differentiation and inhibits endothelial tube formation. Furthermore, at an early stage of differentiation, TGF-β1 may induce in vitro differentiation of hESCs into ECs by inhibiting expression of ID1, while at a later stage of differentiation, TGF-β1 may stimulate the proliferation and migration of ECs via the ALK1/Smad1/5/ID1 pathway. Downregulation of ID1 by gene silencing can lead to acceleration of TGF-β1-induced hESC differentiation into ECs and inhibition of proliferation and migration of ECs. This study may reveal some mechanisms of in vivo vasculogenesis in the early stages of embryonic development.
ID1可介导转化生长因子-β（TGF-β）/激活素受体样激酶-1（ALK1）诱导的（且依赖Smad的）内皮细胞（ECs）迁移。然而，ID1在TGF-β1诱导人胚胎干细胞（hESCs）分化为ECs过程中所起的作用仍不清楚。在本研究中，使用了一种hESC分化模型，该模型概括了胚胎发育早期血管生成的发育步骤，以探究这个问题。我们发现，TGF-β1可增加内皮细胞分化并抑制内皮管形成。此外，在分化早期，TGF-β1可能通过抑制ID1的表达诱导hESCs体外分化为ECs，而在分化后期，TGF-β1可能通过ALK1/Smad1/5/ID1途径刺激ECs的增殖和迁移。通过基因沉默下调ID1可导致TGF-β1诱导的hESCs向ECs分化加速，并抑制ECs的增殖和迁移。本研究可能揭示胚胎发育早期体内血管生成的一些机制。
