Human Blastoids Model Blastocyst Development and Implantation

Overview

Journal Nature

Specialty Science

Date 2021 Dec 2

PMID 34856602

Citations 149

Authors

Harunobu Kagawa

Alok Javali

Heidar Heidari Khoei

Theresa Maria Sommer

Giovanni Sestini

Maria Novatchkova

Yvonne Scholte Op Reimer

Gael Castel

Alexandre Bruneau

Nina Maenhoudt

Jenna Lammers

Sophie Loubersac

Thomas Freour

Hugo Vankelecom

Laurent David

Nicolas Rivron

Affiliations

Soon will be listed here.

Abstract

One week after fertilization, human embryos implant into the uterus. This event requires the embryo to form a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model that we called a blastoid. Here we show that naive human pluripotent stem cells cultured in PXGL medium and triply inhibited for the Hippo, TGF-β and ERK pathways efficiently (with more than 70% efficiency) form blastoids generating blastocyst-stage analogues of the three founding lineages (more than 97% trophectoderm, epiblast and primitive endoderm) according to the sequence and timing of blastocyst development. Blastoids spontaneously form the first axis, and we observe that the epiblast induces the local maturation of the polar trophectoderm, thereby endowing blastoids with the capacity to directionally attach to hormonally stimulated endometrial cells, as during implantation. Thus, we propose that such a human blastoid is a faithful, scalable and ethical model for investigating human implantation and development.

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