Epiblast-like stem cells established by Wnt/β-catenin signaling manifest distinct features of formative pluripotency and germline competence.
Epiblast-like stem cells established by Wnt/β-catenin signaling manifest distinct features of formative pluripotency and germline competence.
复制标题
DOI：
10.1016/j.celrep.2023.112021
复制
发表时间：
2023-01-31
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
不同形成的多能干细胞具有相似的功能特性，近年来被证实是谱系中性和种系胜任的，但具有不同的分子特性。在这里，我们发现WNT/β-catenin信号激活维持了短暂的小鼠上皮样细胞作为上皮样干细胞（EpiLSCs）。EpiLSCs表现出亚稳态形成多能性，具有二价细胞能量代谢和独特的转录组特征和染色质可及性。我们开发了单细胞阶段标签转移（scSTALT）来研究形成性多能连续体，并揭示了EpiLSCs在体内重现了一个独特的发育时期，填补了其他已发表的形成性干细胞之间形成性多能连续体的空白。WNT/β-catenin信号激活通过阻止初始多能性调控网络的完全溶解来抵消activinA和bFGF的分化效应。此外，在FGF受体抑制剂的作用下，EpiLSCs具有直接向种系分化的能力。我们的EpiLSCs可以作为体外模型来模拟和研究胚胎着床后早期发育和多能性转变。Luo等人报道了小鼠上皮细胞样干细胞（EpiLSCs）表现出亚稳态形成多能性，并重现了特定的发育时期。EpiLSCs可作为胚胎着床后发育和多能性转变的体外模型。
Different formative pluripotent stem cells harboring similar functional properties have been recently established to be lineage neutral and germline competent yet have distinct molecular identities. Here, we show that WNT/β-catenin signaling activation sustains transient mouse epiblast-like cells as epiblast-like stem cells (EpiLSCs). EpiLSCs display metastable formative pluripotency with bivalent cellular energy metabolism and unique transcriptomic features and chromatin accessibility. We develop single-cell stage label transfer (scSTALT) to study the formative pluripotency continuum and reveal that EpiLSCs recapitulate a unique developmental period in vivo, filling the gap of the formative pluripotency continuum between other published formative stem cells. WNT/β-catenin signaling activation counteracts differentiation effects of activinA and bFGF by preventing complete dissolution of naive pluripotency regulatory network. Moreover, EpiLSCs have direct competence toward germline specification, which is further matured by an FGF receptor inhibitor. Our EpiLSCs can serve as an in vitro model for mimicking and studying early post-implantation development and pluripotency transition. Luo et al. report mouse epiblast-like stem cells (EpiLSCs) displaying a metastable formative pluripotency and recapitulating a particular developmental period. EpiLSCs serve as an in vitro model for post-implantation development and pluripotency transition.
登录
查看更多内容
影响因子：
5.9
作者：
Cermola F;D'Aniello C;Tatè R;De Cesare D;Martinez-Arias A;Minchiotti G;Patriarca EJ
通讯作者：
Patriarca EJ
影响因子：
8.8
作者：
Cheng, Shangli;Pei, Yu;Deng, Qiaolin
通讯作者：
Deng, Qiaolin
影响因子：
16.6
作者：
Agudelo, Leandro Z.;Ferreira, Duarte M. S.;Ruas, Jorge L.
通讯作者：
Ruas, Jorge L.
影响因子：
64.8
作者：
Chang, Hannah H.;Hemberg, Martin;Huang, Sui
通讯作者：
Huang, Sui
鉴定 ALPPL2 作为人类初始多能性调节所必需的初始多能状态特异性表面蛋白。
影响因子：
8.8
作者：
Bi, Yan;Tu, Zhifen;Gao, Shaorong
通讯作者：
Gao, Shaorong