Cell surface fluctuations regulate early embryonic lineage sorting

Yanagida, Akira; Corujo-Simon, Elena; Revell, Christopher; Sahu, Preeti; Stirparo, Giuliano Giuseppe; Aspalter, Irene M.; Winkel, Alex K; Peters, Ruby; Belly, Henry De; Cassani, Davide A. D.; Achouri, Sarra; Blumenfeld, Raphaël; Franze, Kristian; Hannezo, Édouard; Paluch, Ewa K.; Nichols, Jennifer; Chalut, Kevin J.

doi:10.1016/j.cell.2022.01.022

Cited by 54 publications

(48 citation statements)

References 95 publications

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“…The outcome of cell sorting has been modelled previously by considering cell-specific differences in interfacial energies maximizing the most energetically favourable cell interfaces 15 , 33 – 36 . Disparity in interfacial energy was considered to reflect adhesion differences, with cadherins being the best-characterized effectors 1 , 37 , as espoused in the differential adhesion hypothesis (DAH) 33 , 38 .…”

Section: Mainmentioning

confidence: 99%

Stem cell-derived synthetic embryos self-assemble by exploiting cadherin codes and cortical tension

et al. 2022

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Mammalian embryos sequentially differentiate into trophectoderm and an inner cell mass, the latter of which differentiates into primitive endoderm and epiblast. Trophoblast stem (TS), extraembryonic endoderm (XEN) and embryonic stem (ES) cells derived from these three lineages can self-assemble into synthetic embryos, but the mechanisms remain unknown. Here, we show that a stem cell-specific cadherin code drives synthetic embryogenesis. The XEN cell cadherin code enables XEN cell sorting into a layer below ES cells, recapitulating the sorting of epiblast and primitive endoderm before implantation. The TS cell cadherin code enables TS cell sorting above ES cells, resembling extraembryonic ectoderm clustering above epiblast following implantation. Whereas differential cadherin expression drives initial cell sorting, cortical tension consolidates tissue organization. By optimizing cadherin code expression in different stem cell lines, we tripled the frequency of correctly formed synthetic embryos. Thus, by exploiting cadherin codes from different stages of development, lineage-specific stem cells bypass the preimplantation structure to directly assemble a postimplantation embryo.

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Section: Mainmentioning

confidence: 99%

Stem cell-derived synthetic embryos self-assemble by exploiting cadherin codes and cortical tension

et al. 2022

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“…The exit from naïve pluripotency in vivo is accompanied by a substantial increase in molecular and phenotypic cell heterogeneity. Cellular heterogeneity, in terms of gene expression and morphology, was observed since the formation of the ICM in mouse blastocysts [ 62 , 63 , 64 ]. Similar changes accompany the transition from naïve ESCs to PiCs as well as the generation of other intermediate states of pluripotency, including RSCs [ 3 ] and intermediate epiblast stem cells (IESCs) [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although naïve ESC-derived aggregates appear to be highly homogenous, round-shaped and compacted, PiCs generate loosely packed aggregates that are more irregular and disorganized [ 35 , 40 ]. Although a further analysis is needed, this phenotype may be explained, in part, by the heterogeneity of PiCs; only a fraction/subpopulation of PiCs might be able to engage in stable cell–cell interactions based on a cytoskeleton organization [ 73 ] and/or cell surface dynamics/fluctuations [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Capturing Transitional Pluripotency through Proline Metabolism

Minchiotti

D’Aniello

Fico

et al. 2022

Cells

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In this paper, we summarize the current knowledge of the role of proline metabolism in the control of the identity of Embryonic Stem Cells (ESCs). An imbalance in proline metabolism shifts mouse ESCs toward a stable naïve-to-primed intermediate state of pluripotency. Proline-induced cells (PiCs), also named primitive ectoderm-like cells (EPLs), are phenotypically metastable, a trait linked to a rapid and reversible relocalization of E-cadherin from the plasma membrane to intracellular membrane compartments. The ESC-to-PiC transition relies on the activation of Erk and Tgfβ/Activin signaling pathways and is associated with extensive remodeling of the transcriptome, metabolome and epigenome. PiCs maintain several properties of naïve pluripotency (teratoma formation, blastocyst colonization and 3D gastruloid development) and acquire a few traits of primed cells (flat-shaped colony morphology, aerobic glycolysis metabolism and competence for primordial germ cell fate). Overall, the molecular and phenotypic features of PiCs resemble those of an early-primed state of pluripotency, providing a robust model to study the role of metabolic perturbations in pluripotency and cell fate decisions.

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“…Force fluctuations are functionally significant in numerous biological contexts, such as embryonic lineage sorting [137] , cell migration [138] , and signal transduction [3] . During embryonic development, primitive endoderm (PrE, founder of the yolk sac) and ectoderm (EPI, founder of the fetus) need to be physically separated.…”

Section: Perspectivesmentioning

confidence: 99%

“…During embryonic development, primitive endoderm (PrE, founder of the yolk sac) and ectoderm (EPI, founder of the fetus) need to be physically separated. Dynamic cell surface fluctuations, rather than static cell surface parameters, robustly ensure physical lineage sorting [137] . During cell adhesion, the integrin-based focal adhesions (FAs) exhibit dynamic fluctuating traction through extracellular matrix cytoskeleton motion [138] .…”

Section: Perspectivesmentioning

confidence: 99%