Induction of Mouse Totipotent Stem Cells by a Defined Chemical Cocktail

Overview

Journal Nature

Specialty Science

Date 2022 Jun 21

PMID 35728625

Authors

Yanyan Hu

Yuanyuan Yang

Pengcheng Tan

Yuxia Zhang

Mengxia Han

Jiawei Yu

Xin Zhang

Zeran Jia

Dan Wang

Ke Yao

Huanhuan Pang

Zeping Hu

Yinqing Li

Tianhua Ma

Kang Liu

Sheng Ding

Affiliations

Soon will be listed here.

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 organism. However, it remains unknown whether and how totipotent stem cells can be established in vitro in the absence of germline cells. Here we demonstrate the induction and long-term maintenance of TotiSCs from mouse pluripotent stem cells using a combination of three small molecules: the retinoic acid analogue TTNPB, 1-azakenpaullone and the kinase blocker WS6. The resulting chemically induced totipotent stem cells (ciTotiSCs), resembled mouse totipotent 2-cell embryo cells at the transcriptome, epigenome and metabolome levels. 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 embryos, ciTotiSCs contributed to both embryonic and extraembryonic lineages with high efficiency. Our chemical approach to totipotent stem cell induction and maintenance provides a defined in vitro system for manipulating and developing understanding of the totipotent state and the development of multicellular organisms from non-germline cells.

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