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Derivation of totipotent-like stem cells with blastocyst-like structure forming potential
Cell Research ( IF 44.1 ) Pub Date : 2022-05-04 , DOI: 10.1038/s41422-022-00668-0
Yaxing Xu 1 , Jingru Zhao 1 , Yixuan Ren 1 , Xuyang Wang 1 , Yulin Lyu 2 , Bingqing Xie 1 , Yiming Sun 2 , Xiandun Yuan 3 , Haiyin Liu 1 , Weifeng Yang 4 , Yenan Fu 5 , Yu Yu 5 , Yinan Liu 6 , Rong Mu 3 , Cheng Li 2 , Jun Xu 6 , Hongkui Deng 1
Affiliation  

It is challenging to derive totipotent stem cells in vitro that functionally and molecularly resemble cells from totipotent embryos. Here, we report that a chemical cocktail enables the derivation of totipotent-like stem cells, designated as totipotent potential stem (TPS) cells, from 2-cell mouse embryos and extended pluripotent stem cells, and that these TPS cells can be stably maintained long term in vitro. TPS cells shared features with 2-cell mouse embryos in terms of totipotency markers, transcriptome, chromatin accessibility and DNA methylation patterns. In vivo chimera formation assays show that these cells have embryonic and extraembryonic developmental potentials at the single-cell level. Moreover, TPS cells can be induced into blastocyst-like structures resembling preimplantation mouse blastocysts. Mechanistically, inhibition of HDAC1/2 and DOT1L activity and activation of RARγ signaling are important for inducing and maintaining totipotent features of TPS cells. Our study opens up a new path toward fully capturing totipotent stem cells in vitro.



中文翻译:

具有胚泡样结构形成潜力的全能样干细胞的衍生

在体外获得在功能和分子上类似于来自全能胚胎的细胞的全能干细胞具有挑战性。在这里,我们报告了一种化学混合物能够从 2 细胞小鼠胚胎和扩展的多能干细胞中衍生出全能样干细胞,称为全能潜能干 (TPS) 细胞,并且这些 TPS 细胞可以长期稳定地维持。体外术语。TPS 细胞在全能性标记、转录组、染色质可及性和 DNA 甲基化模式方面与 2 细胞小鼠胚胎具有相同的特征。体内嵌合体形成测定表明,这些细胞在单细胞水平上具有胚胎和胚胎外发育潜力。此外,TPS 细胞可以被诱导成类似于植入前小鼠囊胚的囊胚样结构。机械地,抑制 HDAC1/2 和 DOT1L 活性以及激活 RARγ 信号传导对于诱导和维持 TPS 细胞的全能特性很重要。我们的研究开辟了一条在体外完全捕获全能干细胞的新途径。

更新日期:2022-05-04
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