Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids
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Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids. / Hashmi, Ali; Tlili, Sham; Perrin, Pierre; Lowndes, Molly; Peradziryi, Hanna; Brickman, Joshua M.; Martínez Arias, Alfonso; Lenne, Pierre François.
In: eLife, Vol. 11, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids
AU - Hashmi, Ali
AU - Tlili, Sham
AU - Perrin, Pierre
AU - Lowndes, Molly
AU - Peradziryi, Hanna
AU - Brickman, Joshua M.
AU - Martínez Arias, Alfonso
AU - Lenne, Pierre François
N1 - Publisher Copyright: © 2022, Hashmi et al.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - developmental biology
KW - embryonic stem cells
KW - gastrulation
KW - morphogenesis
KW - mouse
KW - self-organization
U2 - 10.7554/eLife.59371
DO - 10.7554/eLife.59371
M3 - Journal article
C2 - 35404233
AN - SCOPUS:85129345063
VL - 11
JO - eLife
JF - eLife
SN - 2050-084X
ER -
ID: 307330710