Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids
- Aix Marseille University, CNRS, France
- University of Copenhagen, Denmark
- Universitat Pompeu Fabra, Spain
Abstract
Shaping the animal body plan is a complex process that involves the spatial organization and patterning of the different germ layers. Recent advances in live imaging have started to unravel the cellular choreography underlying this process in mammals, however, the sequence of events transforming an unpatterned cell ensemble into structured territories is largely unknown. Here, using gastruloids -3D aggregates of mouse embryonic stem cells- we study the formation of one of the three germ layers, the endoderm. We show that the endoderm is generated from an epiblast-like homogeneous state by a three-step mechanism: (i) a loss of E-cadherin mediated contacts in parts of the aggregate leading to the appearance of islands of E-cadherin expressing cells surrounded by cells devoid of E-cadherin, (ii) a separation of these two populations with islands of E-cadherin expressing cells flowing toward the aggregate tip, and (iii) their differentiation into an endoderm population. During the flow, the islands of E-cadherin expressing cells are surrounded by cells expressing T-Brachyury, reminiscent of the process occurring at the primitive streak. Consistent with recent in vivo observations, the endoderm formation in the gastruloids does not require an epithelial-to-mesenchymal transition, but rather a maintenance of an epithelial state for a subset of cells coupled with fragmentation of E-cadherin contacts in the vicinity, and a sorting process. Our data emphasize the role of signaling and tissue flows in the establishment of the body plan.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. The source data and the scripts at https://zenodo.org/record/5727050
Article and author information
Author details
Pierre-François Lenne
Funding
Agence Nationale de la Recherche (ANR-19-CE13-0022)
- Pierre-François Lenne
Agence Nationale de la Recherche (ANR-11-LABX-0054)
- Ali Hashmi
- Pierre-François Lenne
Agence Nationale de la Recherche (ANR-16-CONV-0001)
- Pierre-François Lenne
Agence Nationale de la Recherche (ANR-10-INBS-04)
- Sham Tlili
- Pierre-François Lenne
Leverhulme Trust (VP2-2015-022)
- Pierre-François Lenne
Leverhulme Trust (RPG- 2018-356)
- Pierre-François Lenne
Lundbeckfonden (R198-2015-412)
- Joshua M Brickman
Novo Nordisk Foundation Center for Basic Metabolic Research (NNF21CC0073729)
- Joshua M Brickman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Isabelle Migeotte, Université Libre de Bruxelles, Belgium
Version history
- Preprint posted: May 24, 2020 (view preprint)
- Received: May 27, 2020
- Accepted: April 8, 2022
- Accepted Manuscript published: April 11, 2022 (version 1)
- Version of Record published: April 22, 2022 (version 2)
Copyright
© 2022, Hashmi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids
eLife 11:e59371.
https://doi.org/10.7554/eLife.59371
