Collaboration between WNT and BMP signaling promotes hemoangiogenic cell development from human fibroblast-derived iPS cells.
Collaboration between WNT and BMP signaling promotes hemoangiogenic cell development from human fibroblast-derived iPS cells.
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WNT 和 BMP 信号传导之间的协作促进人成纤维细胞衍生的 iPS 细胞发育成血管生成细胞。
DOI：
10.1016/j.scr.2010.03.002
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发表时间：
2010
影响因子：
1.2
通讯作者：
Nakayama,Naoki
中科院分区：
文献类型：
--
作者：
Wang,Yi;Umeda,Katsutsugu;Nakayama,Naoki
诱导性多能干细胞（iPS）是通过将成熟细胞核重编程为多能状态而产生的，并显示胚胎干细胞（ES）的生物学特性。人（h）ES细胞在无血清环境中分化5- 8天期间通过WNT和BMP信号传导产生血血管生成后代，其定义为KDR的高水平表达和PDGFRα的低水平表达（KDR+PDGFRαlo），这一观察结果使我们研究hiPS细胞如何产生血血管生成后代。在存在WNT 3a的情况下，4种来源于人皮肤成纤维细胞的hiPS细胞系通常在分化第8天产生KDR+和/或PDGFRα+子代。内源性BMP信号传导是造血细胞发育的WNT 3a定向上调所必需的，并且在所有情况下，血血管生成活性仅限于KDR+PDGFRαlofraction。因此，来源于人皮肤成纤维细胞的iPS细胞在体外生成造血细胞和内皮细胞方面类似于hES细胞。
Induced pluripotent stem (iPS) cells are generated by nuclear reprogramming of mature cells to a pluripotent state, and show biological properties of embryonic stem (ES) cells. The observation that human (h)ES cells generate hemoangiogenic progeny, defined by their high-level expression of KDR and low-level expression of PDGFRα (KDR+PDGFRαlo) via WNT and BMP signaling during 5-8days of differentiation in a serum-free environment led us to address how hiPS cells give rise to hemoangiogenic progeny. In the presence of WNT3a, four hiPS cell lines derived from human skin fibroblasts commonly generated KDR+and/or PDGFRα+progeny by day 8 of differentiation. Endogenous BMP signaling was required for the WNT3a-directed upregulation of hemogenic cell development and the hemoangiogenic activity was confined in all cases to the KDR+PDGFRαlofraction. Thus, iPS cells derived from human skin fibroblasts resemble hES cells in the generation of hematopoietic and endothelial cells in vitro.