Distinctive Roles of Canonical and Noncanonical Wnt Signaling in Human Embryonic Cardiomyocyte Development.
Distinctive Roles of Canonical and Noncanonical Wnt Signaling in Human Embryonic Cardiomyocyte Development.
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DOI：
10.1016/j.stemcr.2016.08.008
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发表时间：
2016-10-11
影响因子：
5.9
通讯作者：
Hoppler, Stefan
中科院分区：
文献类型：
--
作者：
Mazzotta, Silvia;Neves, Carlos;Bonner, Rory J.;Bernardo, Andreia S.;Docherty, Kevin;Hoppler, Stefan
Wnt信号是脊椎动物心脏发育的关键调节因子，然而，对人类心肌细胞发育的具体作用仍不确定。在这里，我们使用人类胚胎干细胞（hESC）系统地分析在人类心肌细胞发育的内源性Wnt信号传导成分的表达，监测途径的活动，并使用小分子抑制剂解剖特定阶段的要求规范和非规范Wnt信号传导机制。我们的分析表明，WNT 3和WNT 8A，通过FZD 7和经典信号，调节BRACHYURY表达和中胚层诱导; WNT 5A/5 B，通过ROR 2和非经典信号，调节MESP 1表达和心血管发育;在发育后期，WNT 2，WNT 5A/5 B和WNT 11，通过FZD 4和FZD 6，通过非经典Wnt信号调节功能性心肌细胞分化。我们的研究结果证实了在人类发育中先前提出的脊椎动物心肌发生的顺序阶段的经典Wnt信号的作用，并确定了更精确的作用，非经典信号和个人Wnt信号和Wnt受体基因在人类心肌细胞发育。hESC用于研究人心肌细胞发育过程中的Wnt信号传导先前提出的经典Wnt信号传导的作用在人中得到证实，在心肌发生中鉴定了非经典Wnt信号传导的特定作用在人心肌发生中鉴定了个体Wnt信号传导和受体基因Wnt信号传导是脊椎动物心脏发育的既定关键调节因子，但其在人心肌细胞发育中的作用仍不清楚。在这里，Hoppler及其同事使用hESC研究经典和非经典Wnt通路活性，并在人类心肌细胞发育过程中鉴定Wnt信号和受体基因。他们确定了与先天性缺陷研究和再生医学应用相关的Wnt信号传导的作用。
Wnt signaling is a key regulator of vertebrate heart development; however, specific roles for human cardiomyocyte development remain uncertain. Here we use human embryonic stem cells (hESCs) to analyze systematically in human cardiomyocyte development the expression of endogenous Wnt signaling components, monitor pathway activity, and dissect stage-specific requirements for canonical and noncanonical Wnt signaling mechanisms using small-molecule inhibitors. Our analysis suggests that WNT3 and WNT8A, via FZD7 and canonical signaling, regulate BRACHYURY expression and mesoderm induction; that WNT5A/5B, via ROR2 and noncanonical signaling, regulate MESP1 expression and cardiovascular development; and that later in development WNT2, WNT5A/5B, and WNT11, via FZD4 and FZD6, regulate functional cardiomyocyte differentiation via noncanonical Wnt signaling. Our findings confirm in human development previously proposed roles for canonical Wnt signaling in sequential stages of vertebrate cardiomyogenesis, and identify more precise roles for noncanonical signaling and for individual Wnt signal and Wnt receptor genes in human cardiomyocyte development. hESCs were used to study Wnt signaling during human cardiomyocyte development Previously proposed roles for canonical Wnt signaling were confirmed in human Specific roles for noncanonical Wnt signaling were identified in cardiomyogenesis Individual Wnt signal and receptor genes were identified in human cardiomyogenesis Wnt signaling is an established key regulator of vertebrate heart development, but its role in human cardiomyocyte development remains unclear. Here, Hoppler and colleagues use hESCs to study canonical and noncanonical Wnt pathway activity and identify Wnt signal and receptor genes during human cardiomyocyte development. They identify roles for Wnt signaling that are relevant for congenital defects studies and regenerative medicine applications.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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DOI：
10.1073/pnas.0402802101
发表时间：
2004-06-22
影响因子：
11.1
作者：
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通讯作者：
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作者：
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