Cell surface fluctuations regulate early embryonic lineage sorting

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

doi:10.1101/2020.08.16.250084

Cited by 8 publications

(6 citation statements)

References 42 publications

(49 reference statements)

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“…These cells have been generated and kindly given to us by Ian Rosewell (Francis Crick Institute, under Holger Gerhardts project license). Dox-inducible IRES mCherry Ezrin_CA & RhoA_CA ES ( Yanagida et al., 2020 ) cells were kindly given to us by Ayaka Yanagida from the Chalut and Nichols’s lab. The EZR_CA was engineered using a PiggyBac system with E14 ES cells.…”

Section: Methodsmentioning

confidence: 99%

Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate

et al. 2021

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Summary Cell fate transitions are frequently accompanied by changes in cell shape and mechanics. However, how cellular mechanics affects the instructive signaling pathways controlling cell fate is poorly understood. To probe the interplay between shape, mechanics, and fate, we use mouse embryonic stem cells (ESCs), which change shape as they undergo early differentiation. We find that shape change is regulated by a β-catenin-mediated decrease in RhoA activity and subsequent decrease in the plasma membrane tension. Strikingly, preventing a decrease in membrane tension results in early differentiation defects in ESCs and gastruloids. Decreased membrane tension facilitates the endocytosis of FGF signaling components, which activate ERK signaling and direct the exit from the ESC state. Increasing Rab5a-facilitated endocytosis rescues defective early differentiation. Thus, we show that a mechanically triggered increase in endocytosis regulates early differentiation. Our findings are of fundamental importance for understanding how cell mechanics regulates biochemical signaling and therefore cell fate.

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Section: Methodsmentioning

confidence: 99%

Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate

et al. 2021

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“…5I). Overall, this suggests DP nEnd is a good model for blastocyst stage PrE just prior to commitment 32,60 .…”

Section: B C)mentioning

confidence: 83%

Enhancer status in the primitive endoderm supports unrestricted lineage plasticity in regulative development

Linneberg-Agerholm

Sell

Riveiro

et al. 2023

Preprint

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Mammalian blastocyst formation involves the specification of trophectoderm followed by the differentiation of the inner cell mass into either epiblast or primitive endoderm. During this time, the embryo maintains a window of plasticity and can redirect its cellular fate when challenged experimentally. In this context, we found that the primitive endoderm alone was sufficient to regenerate a complete blastocyst and continue normal postimplantation development to term. We identify an in vitro population similar to the early primitive endoderm in vivo, that exhibits the same embryonic and extra-embryonic potency, forming three dimensional embryoid structures. Commitment in early primitive endoderm is suppressed by JAK/STAT signalling, collaborating with OCT4 to safeguard enhancer status enabling multi-lineage differentiation. Our observations support the notion that transcription factor persistence underlies plasticity in regulative development and highlights the importance of primitive endoderm in perturbed development.

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“…Although this mechanism escapes the limitations of morphogens, there is no in-depth study on how cells move physically and the source of driving force. A computational model of cell sorting indicated that the asymmetric affinity between EPI and PrE cells is not enough to complete spatial isolation in mouse embryos 28, 29 . Our results show that in addition to the differential adhesion between EPI and PrE cells, energy input mediated by the mechanical vibration of the cavity is required to complete the segregation of the spatial location.…”

Section: Discussionmentioning

confidence: 99%

Brazil Nut Effect Drives Pattern Formation in Early Mammalian Embryos

Guo

Yao

Zheng

et al. 2021

Preprint

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Since early mammalian embryos lack chemical gradients, the pattern formation mechanism is an open question. During the second cell fate decision of mouse embryos, the inner cell mass (ICM) segregates into topographically regionalized epiblast (EPI) and primitive endoderm (PrE) layers. Here, we report that the cell segregation process coincides with an emerged periodic expansion-contraction vibration of the blastocyst cavity, which induces a phase transition in the ICM compartment to a higher fluidity state. By experiments and modeling, we demonstrate that the spatial segregation of PrE and EPI precursors is mediated by a "Brazil nut effect"-like viscous segregation mechanism in which the vibration of the cavity induces cyclic directional tissue flows in the compartment of the ICM, which drives the separation and asymmetric migration of PrE and EPI precursors through granular segregation biased by different levels of particle adhesivity and sizes. Furthermore, cyclic embryo vibration also regulates the gene expression of PrE and EPI precursors through mechanotransduction by YAP. Our findings unveil a fundamental mechanism for ensuring the robustness of cell segregation and pattern formation, which is driven by the global geometry and mechanical behavior of early embryos.

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Cell surface fluctuations regulate early embryonic lineage sorting

Cited by 8 publications

References 42 publications

Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate

Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate

Enhancer status in the primitive endoderm supports unrestricted lineage plasticity in regulative development

Brazil Nut Effect Drives Pattern Formation in Early Mammalian Embryos

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