ER71 acts downstream of BMP, Notch, and Wnt signaling in blood and vessel progenitor specification
ER71 acts downstream of BMP, Notch, and Wnt signaling in blood and vessel progenitor specification
复制标题
DOI：
10.1016/j.stem.2008.03.008
复制
发表时间：
2008-05-01
期刊：
影响因子：
23.9
通讯作者：
Choi, Kyunghee
中科院分区：
文献类型：
--
作者：
Lee, Dongjun;Park, Changwon;Choi, Kyunghee
表达FLK 1（+）的中胚层产生血液和血管。在这里，我们表明，BMP，Notch和Wnt信号的组合是必需的有效FLK 1（+）胚胎干细胞（ESC）中胚层形成。BMP、Notch和Wnt信号通路的抑制大大降低了FLK 1（+）中胚层的生成和Ets转录因子Er 71的表达。ESCs中ER 71的增强表达导致FLK 1（+）中胚层的强烈诱导;当被BMP、Notch和Wnt抑制剂阻断时，拯救了FLK 1（+）中胚层的产生;并增强了造血和内皮细胞的产生。Er 71缺陷小鼠FLK 1表达大大减少，在妊娠早期死亡，并显示出严重的血液和血管缺陷，这是高度联想到Flk 1 null小鼠表型。总的来说，我们提供了令人信服的证据，ER 71的功能下游的BMP，Notch和Wnt信号和调节FLK 1（+）中胚层，血液和血管的发展。
FLK1-expressing (FLK1(+)) mesoderm generates blood and vessels. Here, we show that combined BMP, Notch, and Wnt signaling is necessary for efficient FLK1(+) mesoderm formation from embryonic stem cells (ESCs). Inhibition of BMP, Notch, and Wnt signaling pathways greatly decreased the generation of FLK1(+) mesoderm and expression of the Ets transcription factor Er71. Enforced expression of ER71 in ESCs resulted in a robust induction of FLK1(+) mesoderm; rescued the generation of FLK1(+) mesoderm when blocked by BMP, Notch, and Wnt inhibition; and enhanced hematopoietic and endothelial cell generation. Er71-deficient mice had greatly reduced FLK1 expression, died early in gestation, and displayed severe blood and vessel defects that are highly reminiscent of the Flk1 null mouse phenotype. Collectively, we provide compelling evidence that ER71 functions downstream of BMP, Notch, and Wnt signals and regulates FLK1(+) mesoderm, blood, and vessel development.