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Pluripotent state transitions coordinate morphogenesis in mouse and human embryos

Research output: Contribution to journalLetter

Marta N. Shahbazi, Antonio Scialdone, Natalia Skorupska, Antonia Weberling, Gaelle Recher, Meng Zhu, Agnieszka Jedrusik, Liani G. Devito, Laila Noli, Iain C. MacAulay, Christa Buecker, Yakoub Khalaf, Dusko Ilic, Thierry Voet, John C. Marioni, Magdalena Zernicka-Goetz

Original languageEnglish
Article number7684
Pages (from-to)239-243
Number of pages5
JournalNATURE
Volume552
Early online date29 Nov 2017
DOIs
Publication statusPublished - 14 Dec 2017

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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.

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