Haploid-genetic Screening of Trophectoderm Specification Identifies As a Repressor of Totipotent-like Status

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Dec 20

PMID 38117886

Authors

Wenhao Zhang

Shengyi Sun

Qing Wang

Xu Li

Mei Xu

Qian Li

Yiding Zhao

Keli Peng

Chunmeng Yao

Yuna Wang

Ying Chang

Yan Liu

Xudong Wu

Qian Gao

Ling Shuai

Affiliations

Soon will be listed here.

Abstract

Trophectoderm (TE) and the inner cell mass are the first two lineages in murine embryogenesis and cannot naturally transit to each other. The barriers between them are unclear and fascinating. Embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) retain the identities of inner cell mass and TE, respectively, and, thus, are ideal platforms to investigate these lineages in vitro. Here, we develop a loss-of-function genetic screening in haploid ESCs and reveal many mutations involved in the conversion of TSCs. The disruption of either or (candidates) in ESCs facilitates the conversion of TSCs. According to transcriptome analysis, we find that the repression of activates totipotency, which is a possible reason for TE specification. -null ESCs can contribute to embryonic and extraembryonic tissues in chimeras and can efficiently form blastocyst-like structures, indicating their totipotent developmental abilities. These findings provide insights into the mechanisms underlying cell fate alternation in embryogenesis.

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