Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids
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...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/59371 |
| _version_ | 1811252315989999616 |
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| author | Ali Hashmi Sham Tlili Pierre Perrin Molly Lowndes Hanna Peradziryi Joshua M Brickman Alfonso Martínez Arias Pierre-François Lenne |
| author_facet | Ali Hashmi Sham Tlili Pierre Perrin Molly Lowndes Hanna Peradziryi Joshua M Brickman Alfonso Martínez Arias Pierre-François Lenne |
| author_sort | Ali Hashmi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:33:53Z |
| format | Article |
| id | doaj.art-6838f1551a514f58bb1a4c41888aafa4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:33:53Z |
| publishDate | 2022-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6838f1551a514f58bb1a4c41888aafa42022-12-22T03:25:04ZengeLife Sciences Publications LtdeLife2050-084X2022-04-011110.7554/eLife.59371Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloidsAli Hashmi0https://orcid.org/0000-0001-9946-7679Sham Tlili1https://orcid.org/0000-0001-6018-9923Pierre Perrin2Molly Lowndes3Hanna Peradziryi4Joshua M Brickman5https://orcid.org/0000-0003-1580-7491Alfonso Martínez Arias6https://orcid.org/0000-0002-1781-564XPierre-François Lenne7https://orcid.org/0000-0003-1066-7506Aix-Marseille University, CNRS, UMR 7288, IBDM, Turing Center for Living Systems, Marseille, FranceAix-Marseille University, CNRS, UMR 7288, IBDM, Turing Center for Living Systems, Marseille, FranceAix-Marseille University, CNRS, UMR 7288, IBDM, Turing Center for Living Systems, Marseille, FranceNovo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), University of Copenhagen, Copenhagen, DenmarkDepartment of Genetics, University of Cambridge, Cambridge, United Kingdom; Systems Bioengineering, DCEXS , Universidad Pompeu Fabra, ICREA, Barcelona, SpainAix-Marseille University, CNRS, UMR 7288, IBDM, Turing Center for Living Systems, Marseille, FranceShaping 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.https://elifesciences.org/articles/59371morphogenesisgastrulationembryonic stem cellsself-organization |
| spellingShingle | Ali Hashmi Sham Tlili Pierre Perrin Molly Lowndes Hanna Peradziryi Joshua M Brickman Alfonso Martínez Arias Pierre-François Lenne Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids eLife morphogenesis gastrulation embryonic stem cells self-organization |
| title | Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids |
| title_full | Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids |
| title_fullStr | Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids |
| title_full_unstemmed | Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids |
| title_short | Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids |
| title_sort | cell state transitions and collective cell movement generate an endoderm like region in gastruloids |
| topic | morphogenesis gastrulation embryonic stem cells self-organization |
| url | https://elifesciences.org/articles/59371 |
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