A Gastruloid Model of the Interaction Between Embryonic and Extra-embryonic Cell Types

Overview

Journal J Tissue Eng

Date 2022 Jun 16

PMID 35707767

Authors

Noemie Mlp Berenger-Currias

Maria Mircea

Esmee Adegeest

Patrick R van den Berg

Marleen Feliksik

Mazene Hochane

Timon Idema

Sander J Tans

Stefan Semrau

Affiliations

Soon will be listed here.

Abstract

Stem-cell derived in vitro systems, such as organoids or embryoids, hold great potential for modeling in vivo development. Full control over their initial composition, scalability, and easily measurable dynamics make those systems useful for studying specific developmental processes in isolation. Here we report the formation of gastruloids consisting of mouse embryonic stem cells (mESCs) and extraembryonic endoderm (XEN) cells. These XEN-enhanced gastruloids (XEGs) exhibit the formation of neural epithelia, which are absent in gastruloids derived from mESCs only. By single-cell RNA-seq, imaging, and differentiation experiments, we demonstrate the neural characteristics of the epithelial tissue. We further show that the mESCs induce the differentiation of the XEN cells to a visceral endoderm-like state. Finally, we demonstrate that local inhibition of WNT signaling and production of a basement membrane by the XEN cells underlie the formation of the neuroepithelial tissue. In summary, we establish XEGs to explore heterotypic cellular interactions and their developmental consequences in vitro.

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