Abscission Couples Cell Division to Embryonic Stem Cell Fate.

Agathe Chaigne,Meghan Agnew,Céline Labouesse,Ian J White,Ewa K Paluch,Edouard Hannezo,Kevin J Chalut

doi:10.1016/j.devcel.2020.09.001

Abstract

SummaryCell fate transitions are key to development and homeostasis. It is thus essential to understand the cellular mechanisms controlling fate transitions. Cell division has been implicated in fate decisions in many stem cell types, including neuronal and epithelial progenitors. In other stem cells, such as embryonic stem (ES) cells, the role of division remains unclear. Here, we show that exit from naive pluripotency in mouse ES cells generally occurs after a division. We further show that exit timing is strongly correlated between sister cells, which remain connected by cytoplasmic bridges long after division, and that bridge abscission progressively accelerates as cells exit naive pluripotency. Finally, interfering with abscission impairs naive pluripotency exit, and artificially inducing abscission accelerates it. Altogether, our data indicate that a switch in the division machinery leading to faster abscission regulates pluripotency exit. Our study identifies abscission as a key cellular process coupling cell division to fate transitions.

Highlights

During embryonic development and in adult tissue homeostasis, cell fate transitions allow the generation and maintenance of the diversity of cells constituting a functioning organism
We find that abscission, the last stage of cell division, when sister cells become physically separated, is slow in naive embryonic stem (ES) cells, which remain connected by cytoplasmic bridges for a long time after division
We used ES cells expressing a short half-life naive pluripotency reporter REX1-GFPd2 expressed from the endogenous REX1 locus (Kalkan et al, 2017; Strawbridge et al, 2020), since REX1 downregulation correlates with naive pluripotency exit (Kalkan et al, 2017; Mulas et al, 2017)

Summary

Introduction

During embryonic development and in adult tissue homeostasis, cell fate transitions allow the generation and maintenance of the diversity of cells constituting a functioning organism. Cell division has been proposed to act as a switch during cellular fate transitions (Williams and Fuchs, 2013). A canonical example of mitotic control of cell fate is the first division of the C. elegans embryo, where cortical cues drive asymmetric spindle positioning, leading to asymmetries between daughter cells crucial for antero-posterior axis specification (Cowan and Hyman, 2004). In Drosophila and C. elegans neuroblasts, asymmetries in polarity determinant distribution correlate with size asymmetries between daughter cells, and in C. elegans, these size asymmetries have been proposed to directly control daughter cell fate after division

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