Derivation of trophoblast stem cells unveils unrestrained potential of mouse ESCs and epiblast

Debabrata Jana; Purnima Sailasree; Priya Singh; Mansi Srivastava; Vijay V. Vishnu; Hanuman T Kale; Jyothi Lakshmi; G. Srinivas; Divya Tej Sowpati; P Chandra Shekar

doi:10.1101/2023.04.19.537518

Developmental BiologybioRxivApr 19, 2023

Preprint

Derivation of trophoblast stem cells unveils unrestrained potential of mouse ESCs and epiblast

Debabrata Jana iD, Purnima Sailasree, Priya Singh iD, Mansi Srivastava iD, Vijay V. Vishnu iD, Hanuman T Kale iD, Jyothi Lakshmi, G. Srinivas iD, Divya Tej Sowpati iD, P Chandra Shekar iD

Abstract

mESCs and epiblast are considered to follow strict lineage adherence and lack the potential to contribute to trophoectoderm. Here, we report the derivation of trophoblast stem cells (ESTS) from the mESCs. The single-cell transcriptome and molecular characterization of ESTS show similarity with TSCs. They efficiently integrate into the TE compartment of the blastocyst and contribute to the placenta during development. We discovered GSK3{beta} as a critical regulator of the TE fate of ESCs. It plays a vital stage-specific role during ESTS derivation. We further show {beta}-CATENIN and an intron-I regulatory element of Cdx2 are essential for the TE fate of ESCs. We further show that the mouse epiblast can readily differentiate into TE lineage. In contrast to the paradigm of the restricted potential of pluripotent ESCs and epiblast, our data shows that murine ESCs and epiblast have the unrestrained developmental potential for extraembryonic lineages.

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