小柯机器人

清华大学丁胜等研究人员合作利用确定的化学混合物诱导出小鼠全能干细胞。2022年6月21日，《自然》杂志在线发表了这项成果。

研究人员展示了通过三种小分子，即TTNPB、1-Azakenpaullone和WS6的组合，从小鼠多能干细胞（PSC）中诱导并长期维持全能干细胞（TotiSC）。这些细胞，被命名为ciTotiSC（化学诱导的全能干细胞），在转录组、表观基因组和代谢组水平上与小鼠全能2C胚胎期细胞相似。此外，ciTotiSC表现出双向发育的潜力，能够在体外和畸胎瘤中产生胚胎和胚外细胞。此外，在注射到8细胞的胚胎后，ciTotiSC对胚胎和胚胎外系都有很高的贡献。研究人员对TotiSC的诱导和维持的化学方法提供了一个明确的体外系统，能够操纵和了解全能状态，从非生殖系创造生命。

据介绍，在小鼠中，只有合子和来自2细胞胚胎的卵裂球是真正的TotiSC，能够产生胚胎和胚胎外组织的所有分化细胞，并形成整个机体。然而，在没有生殖细胞的情况下，是否以及如何在体外建立代表生命之初的TotiSC，仍然是一个挑战。

附：英文原文

Title: Induction of mouse totipotent stem cells by a defined chemical cocktail

Author: Hu, Yanyan, Yang, Yuanyuan, Tan, Pengcheng, Zhang, Yuxia, Han, Mengxia, Yu, Jiawei, Zhang, Xin, Jia, Zeran, Wang, Dan, Li, Yinqing, Ma, Tianhua, Liu, Kang, Ding, Sheng

Issue&Volume: 2022-06-21

Abstract: In mice, only the zygotes and blastomeres from 2-cell embryos are authentic totipotent stem cells (TotiSCs), capable of producing all the differentiated cells in both embryonic and extraembryonic tissues and forming an entire organism1. However, it remains challenging whether and how TotiSCs, representing the very beginning of a life, can be established in vitro in the absence of germline cells. Here, we demonstrate induction and long-term maintenance of TotiSCs from mouse pluripotent stem cells (PSCs) by a combination of three small molecules, TTNPB, 1-Azakenpaullone, and WS6. These cells, which we designated as ciTotiSCs (chemically induced totipotent stem cells), resembled mouse totipotent 2C-embryo stage cells at transcriptome, epigenome and metabolome level. In addition, ciTotiSCs exhibited bidirectional developmental potentials and were able to produce both embryonic and extraembryonic cells in vitro and in teratoma. Furthermore, following injection into 8-cell embryo, ciTotiSCs contributed to both embryonic and extraembryonic lineages with high efficiency. Our chemical approach for TotiSCs induction and maintenance provides a defined in vitro system to manipulate and understand totipotent state towards creating life from non-germline.

DOI: 10.1038/s41586-022-04967-9

Source: https://www.nature.com/articles/s41586-022-04967-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html