Embryo model Completes Gastrulation to Neurulation and Organogenesis

Overview

Journal Nature

Specialty Science

Date 2022 Aug 25

PMID 36007540

Authors

Gianluca Amadei

Charlotte E Handford

Chengxiang Qiu

Joachim De Jonghe

Hannah Greenfeld

Martin Tran

Beth K Martin

Dong-Yuan Chen

Alejandro Aguilera-Castrejon

Jacob H Hanna

Michael B Elowitz

Florian Hollfelder

Jay Shendure

David M Glover

Magdalena Zernicka-Goetz

Affiliations

Soon will be listed here.

Abstract

Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem (TS) cells, extraembryonic endoderm stem (XEN) cells and inducible XEN (iXEN) cells. Here we assembled stem cell-derived embryos in vitro from mouse ES cells, TS cells and iXEN cells and showed that they recapitulate the development of whole natural mouse embryo in utero up to day 8.5 post-fertilization. Our embryo model displays headfolds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extraembryonic yolk sac that initiates blood island development. Notably, we demonstrate that the neurulating embryo model assembled from Pax6-knockout ES cells aggregated with wild-type TS cells and iXEN cells recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous Pax6-knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse cell lineages and genes in development. Our results demonstrate the self-organization ability of ES cells and two types of extraembryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis.

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