CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport.
CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport.
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DOI：
10.1038/s41419-022-05184-y
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发表时间：
2022-09-02
影响因子：
9
通讯作者：
Kong, Shuangbo
中科院分区：
文献类型：
--
作者：
Jiang, Ruiwei;Tang, Xiaofang;Pan, Jiale;Li, Gaizhen;Yang, Ningjie;Tang, Yedong;Bi, Shilei;Cai, Han;Chen, Qionghua;Chen, Dunjin;Wang, Haibin;Kong, Shuangbo
纤毛细胞和分泌细胞是构成输卵管上皮的两种主要细胞类型。越来越多的证据支持输卵管多纤毛上皮在胚胎运输中的作用，然而这种特化细胞类型分化的机制仍然难以捉摸。在这里，我们报道了输卵管上皮CDC42的缺失阻碍了多纤毛虫细胞的形态发生，并导致胚胎保留，导致妊娠早期失败。利用输卵管类器官模型，我们进一步观察到CDC42引导分泌细胞转变为多纤体细胞，而不依赖于其GTPase活性和众所周知的Notch通路。进一步的研究发现AKT是多纤体细胞分化不可或缺的新调控因子，其活性由CDC42通过与p110β相互作用维持。同样，在敲除Cdc42的输卵管类器官中，重新激活AKT部分地刺激多纤毛细胞分化。最后，在异位妊娠的女性中，可以观察到低水平的CDC42和磷酸化akt与减少的多纤毛细胞在输卵管中。总之，我们提供了以前未被重视的证据，证明CDC42-AKT信号是输卵管多毛细胞形态发生的关键决定因素，这在理解异位妊娠的病理和促进预防策略的制定方面具有临床应用价值。
Ciliated and secretory cells are two major cell types that comprise the oviduct epithelia. Accumulating evidences support a role of oviductal multiciliated epithelia for embryo transport, however the mechanisms underlying this specialized cell type differentiation remain elusive. Here, we report that CDC42 depletion in oviduct epithelia hampers the morphogenesis of multiciliated cell, and results in embryo retention, leading to early pregnancy failure. Utilizing the oviduct organoid model, we further observed that CDC42 guides secretory cells transition into multiciliated cells independent of its GTPase activity and the well-known Notch pathway. Further exploration uncovered the AKT as a novel indispensable regulator for multiciliated cells differentiation, whose activity was maintained by CDC42 through interacting with the p110β. Consistently, re-activating AKT partially incites multiciliated cells differentiation in Cdc42 knockout oviductal organoids. Finally, low levels of CDC42 and phospho-AKT with reduced multiciliated cells in the oviduct are observed in women with ectopic pregnancy. Collectively, we provide previously unappreciated evidence that CDC42-AKT signaling is a critical determinant for morphogenesis of oviduct multiciliated cell, which possesses the clinical application in understanding the pathology of ectopic pregnancy and facilitating the development of prevention strategies.
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影响因子：
64.5
作者：
Fritsch R;de Krijger I;Fritsch K;George R;Reason B;Kumar MS;Diefenbacher M;Stamp G;Downward J
通讯作者：
Downward J
影响因子：
6.1
作者：
Raidt, Johanna;Werner, Claudius;Omran, Heymut
通讯作者：
Omran, Heymut
增强的 HOXA10 sumoylation 会抑制反复植入失败的女性的胚胎植入。
影响因子：
7
作者：
Jiang R;Ding L;Zhou J;Huang C;Zhang Q;Jiang Y;Liu J;Yan Q;Zhen X;Sun J;Yan G;Sun H
通讯作者：
Sun H
影响因子：
4.6
作者：
Lu, Hao;Anujan, Priyanka;Roy, Sudipto
通讯作者：
Roy, Sudipto
影响因子：
8.8
作者：
Dinh, Huy Q.;Lin, Xianzhi;Abbasi, Forough;Nameki, Robbin;Haro, Marcela;Olingy, Claire E.;Chang, Heidi;Hernandez, Lourdes;Gayther, Simon A.;Wright, Kelly N.;Aspuria, Paul-Joseph;Karlan, Beth Y.;Corona, Rosario, I;Li, Andrew;Rimel, B. J.;Siedhoff, Matthew T.;Medeiros, Fabiola;Lawrenson, Kate
通讯作者：
Lawrenson, Kate