Pluripotent state transitions coordinate morphogenesis in mouse and human embryos.

Abstract:

:The foundations of mammalian development lie in a cluster of embryonic epiblast stem cells. In response to extracellular matrix signalling, these cells undergo epithelialization and create an apical surface in contact with a cavity, a fundamental event for all subsequent development. Concomitantly, epiblast cells transit through distinct pluripotent states, before lineage commitment at gastrulation. These pluripotent states have been characterized at the molecular level, but their biological importance remains unclear. Here we show that exit from an unrestricted naive pluripotent state is required for epiblast epithelialization and generation of the pro-amniotic cavity in mouse embryos. Embryonic stem cells locked in the naive state are able to initiate polarization but fail to undergo lumenogenesis. Mechanistically, exit from naive pluripotency activates an Oct4-governed transcriptional program that results in expression of glycosylated sialomucin proteins and the vesicle tethering and fusion events of lumenogenesis. Similarly, exit of epiblasts from naive pluripotency in cultured human post-implantation embryos triggers amniotic cavity formation and developmental progression. Our results add tissue-level architecture as a new criterion for the characterization of different pluripotent states, and show the relevance of transitions between these states during development of the mammalian embryo.

journal_name

Nature

journal_title

Nature

authors

Shahbazi MN,Scialdone A,Skorupska N,Weberling A,Recher G,Zhu M,Jedrusik A,Devito LG,Noli L,Macaulay IC,Buecker C,Khalaf Y,Ilic D,Voet T,Marioni JC,Zernicka-Goetz M

doi

10.1038/nature24675

subject

Has Abstract

pub_date

2017-12-14 00:00:00

pages

239-243

issue

7684

eissn

0028-0836

issn

1476-4687

pii

nature24675

journal_volume

552

pub_type

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