IP3R-mediated Ca2+ signals govern hematopoietic and cardiac divergence of Flk1+ cells via the calcineurin-NFATc3-Etv2 pathway
IP3R-mediated Ca2+ signals govern hematopoietic and cardiac divergence of Flk1+ cells via the calcineurin-NFATc3-Etv2 pathway
复制标题
IP3R 介导的 Ca2 信号通过钙调神经磷酸酶-NFATc3-Etv2 途径控制 Flk1 细胞的造血和心脏分化
DOI：
10.1093/jmcb/mjx014
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Yang Huang-Tian
中科院分区：
文献类型：
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作者：
Wang YIjie;Huang Jijun;Liu Wenqiang;Kou Xiaochen;Tang Huayuan;Wang Hong;Yu Xiujian;Gao Shaorong;Ouyang Kunfu;Yang Huang-Tian
AbstractsCa2+signals participate in various cellular processes with spatial and temporal dynamics, among which, inositol 1,4,5-trisphosphate receptors (IP3Rs)-mediated Ca2+signals are essential for early development. However, the underlying mechanisms of IP3R-regulated cell fate decision remain largely unknown. Here we report that IP3Rs are required for the hematopoietic and cardiac fate divergence of mouse embryonic stem cells (mESCs). Deletion of IP3Rs (IP3R-tKO) reduced Flk1+/PDGFRα−hematopoietic mesoderm, c-Kit+/CD41+hematopoietic progenitor cell population, and the colony-forming unit activity, but increased cardiac progenitor markers as well as cardiomyocytes. Concomitantly, the expression of a key regulator of hematopoiesis,Etv2, was reduced in IP3R-tKO cells, which could be rescued by the activation of Ca2+signals and calcineurin or overexpression of constitutively active form of NFATc3. Furthermore, IP3R-tKO impaired specific targeting ofEtv2by NFATc3 via its evolutionarily conserved cis-element in differentiating ESCs. Importantly, the activation of Ca2+–calcineurin–NFAT pathway reversed the phenotype of IP3R-tKO cells. These findings reveal an unrecognized governing role of IP3Rs in hematopoietic and cardiac fate commitment via IP3Rs–Ca2+–calcineurin–NFATc3–Etv2 pathway.
