Maine Medical Center, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA.
J Cell Biochem. 2010 Feb 1;109(2):363-74. doi: 10.1002/jcb.22410.
The signals that direct pluripotent stem cell differentiation into lineage-specific cells remain largely unknown. Here, we investigated the roles of BMP on vascular progenitor development from human embryonic stem cells (hESCs). In a serum-free condition, hESCs sequentially differentiated into CD34+CD31-, CD34+CD31+, and then CD34-CD31+ cells during vascular cell development. CD34+CD31+ cells contained vascular progenitor population that gives rise to endothelial cells and smooth muscle cells. BMP4 promoted hESC differentiation into CD34+CD31+ cells at an early stage. In contrast, TGFbeta suppressed BMP4-induced CD34+CD31+ cell development, and promoted CD34+CD31- cells that failed to give rise to either endothelial or smooth muscle cells. The BMP-Smad inhibitor, dorsomorphin, inhibited phosphorylation of Smad1/5/8, and blocked hESC differentiation to CD34+CD31+ progenitor cells, suggesting that BMP Smad-dependent signaling is critical for CD34+CD31+ vascular progenitor development. Our findings provide new insight into how pluripotent hESCs differentiate into vascular cells.
指导多能干细胞分化为谱系特异性细胞的信号在很大程度上仍然未知。在这里，我们研究了 BMP 在人胚胎干细胞（hESC）向血管祖细胞发育中的作用。在无血清条件下，hESC 依次分化为血管细胞发育过程中的 CD34+CD31-、CD34+CD31+，然后是 CD34-CD31+细胞。CD34+CD31+细胞包含血管祖细胞群体，可分化为内皮细胞和平滑肌细胞。BMP4 在早期促进 hESC 分化为 CD34+CD31+细胞。相比之下，TGFbeta 抑制 BMP4 诱导的 CD34+CD31+细胞发育，并促进 CD34+CD31-细胞，这些细胞不能分化为内皮细胞或平滑肌细胞。BMP-Smad 抑制剂 dorsomorphin 抑制 Smad1/5/8 的磷酸化，并阻断 hESC 分化为 CD34+CD31+祖细胞，表明 BMP Smad 依赖性信号对于 CD34+CD31+血管祖细胞的发育至关重要。我们的发现为多能 hESC 如何分化为血管细胞提供了新的见解。
