Hyperactivated Wnt-β-catenin signaling in the absence of sFRP1 and sFRP5 disrupts trophoblast differentiation through repression of Ascl2.
Hyperactivated Wnt-β-catenin signaling in the absence of sFRP1 and sFRP5 disrupts trophoblast differentiation through repression of Ascl2.
复制标题
在缺乏sFRPl和sFRP 5的情况下，过度活化的Wnt-β-连环蛋白信号传导通过Ascl 2的抑制破坏滋养层分化。
DOI：
10.1186/s12915-020-00883-4
复制
发表时间：
2020-10-27
期刊：
影响因子：
5.4
通讯作者：
Lu J
中科院分区：
文献类型：
--
作者：
Bao H;Liu D;Xu Y;Sun Y;Mu C;Yu Y;Wang C;Han Q;Liu S;Cai H;Liu F;Kong S;Deng W;Cao B;Wang H;Wang Q;Lu J
Wnt signaling is a critical determinant for the maintenance and differentiation of stem/progenitor cells, including trophoblast stem cells during placental development. Hyperactivation of Wnt signaling has been shown to be associated with human trophoblast diseases. However, little is known about the impact and underlying mechanisms of excessive Wnt signaling during placental trophoblast development. In the present work, we observed that two inhibitors of Wnt signaling, secreted frizzled-related proteins 1 and 5 (Sfrp1 and Sfrp5), are highly expressed in the extraembryonic trophoblast suggesting possible roles in early placental development. Sfrp1 and Sfrp5 double knockout mice exhibited disturbed trophoblast differentiation in the placental ectoplacental cone (EPC), which contains the precursors of trophoblast giant cells (TGCs) and spongiotrophoblast cells. In addition, we employed mouse models expressing a truncated β-catenin with exon 3 deletion globally and trophoblast-specifically, as well as trophoblast stem cell lines, and unraveled that hyperactivation of canonical Wnt pathway exhausted the trophoblast precursor cells in the EPC, resulting in the overabundance of giant cells at the expense of spongiotrophoblast cells. Further examination uncovered that hyperactivation of canonical Wnt pathway disturbed trophoblast differentiation in the EPC via repressing Ascl2 expression. Our investigations provide new insights that the homeostasis of canonical Wnt-β-catenin signaling is essential for EPC trophoblast differentiation during placental development, which is of high clinical relevance, since aberrant Wnt signaling is often associated with trophoblast-related diseases.
登录
查看更多内容
影响因子：
--
作者：
Jiang, B;Kamat, A;Mendelson, CR
通讯作者：
Mendelson, CR
影响因子：
56.9
作者：
He, TC;Sparks, AB;Kinzler, KW
通讯作者：
Kinzler, KW
影响因子：
30.8
作者：
Anson-Cartwright, L;Dawson, K;Cross, JC
通讯作者：
Cross, JC
影响因子：
14.8
作者：
Lee, Tong Ihn;Johnstone, Sarah E.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
64.8
作者：
GUILLEMOT, F;NAGY, A;JOYNER, AL
通讯作者：
JOYNER, AL