Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors
Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors
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DOI：
10.1073/pnas.0704044104
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发表时间：
2007-06-26
影响因子：
11.1
通讯作者：
Srivastava, Deepak
中科院分区：
文献类型：
--
作者：
Kwon, Chulan;Arnold, Joshua;Srivastava, Deepak
引导多能细胞进入不同的谱系并控制其扩张仍然是发育和干细胞生物学的基本挑战。WRIT途径的成员控制着许多关键的胚胎事件，通常促进祖细胞的自我更新或扩张。相比之下，规范的WRIT配体被认为在几个物种中对心脏发育具有负面调节作用。然而，在心脏前中胚层中，规范的Wnt信号通过其必需的转录中介β-连环蛋白发挥的细胞自主作用尚不清楚。利用组织特异性体内基因操作，我们发现β-连环蛋白是心脏前体细胞发育所必需的，并且是此类前体细胞增殖扩张的正向调节因子。在胚胎干细胞发育的离散窗口，激活规范的WRIT信号促进了最初承诺后心脏前体细胞的扩张，这是心脏分化所必需的。总之，这些数据提供了体内和体外证据，证明规范的WRIT信号促进心脏祖细胞的扩张和心脏细胞的分化。
Guiding multipotent cells into distinct lineages and controlling their expansion remain fundamental challenges in developmental and stem cell biology. Members of the Writ pathway control many pivotal embryonic events, often promoting self-renewal or expansion of progenitor cells. In contrast, canonical Writ ligands are thought to negatively regulate cardiorryogenesis in several species. However, the cell-autonomous role of canonical Wnt signaling within precardiac mesoderm, through its obligatory transcriptional mediator, beta-catenin, is unknown. Using tissue-specific in vivo genetic manipulation, we found that beta-catenin is required for development of cardiac progenitors and is a positive regulator of proliferative expansion of such progenitor cells. At discrete windows of development in embryonic stem cells, activation of canonical Writ signaling promoted expansion of cardiac progenitors after initial commitment and was required for cardiac differentiation. Together, these data provide in vivo and in vitro evidence that canonical Writ signaling promotes the expansion of cardiac progenitors and differentiation of cardiornyocytes.