| 论文题目： | Inhibition of endothelial ERK signalling by Smad1/5 is essential for haematopoietic stem cell emergence |
| 论文题目英文： | |
| 作者： | 张春霞，吕军华，何秋萍，王思峰，高雅，#孟安明，#Yang Xiao，刘峰* |
| 论文出处： | |
| 年： | 2014 |
| 卷： | 5 |
| 期： | 3431 |
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| 联系作者： | 刘峰 |
| 发表期刊： | Nature Communications |
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| 论文连接 | http://www.nature.com/ncomms/2014/140311/ncomms4431/abs/ncomms4431.html#/affil-auth |
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| 摘要: | The earliest HSCs are derived from haemogenic endothelium via endothelial-to-haematopoietic transition during vertebrate embryogenesis; however, the underlying mechanism is largely unclear. Here we show that interplay of Smad1/5 and ERK signalling is essential for haemogenic endothelium-based HSC emergence. Smad1/5 directly inhibits erk expression through recruiting HDAC1 to and inducing de-acetylation of the erk promoter in endothelial cells. Over-activated ERK signalling conferred by inhibition of Smad1/5 promotes the arterial endothelial cell fate and constitutively strengthens the tight junction between endothelial cells, thereby repressing the specification of haemogenic endothelium and the following endothelial-to-haematopoietic transition process. These findings provide new insights into the in vitro generation of transplantable HSCs for potential clinical applications. |
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