Multi-omic Profiling Reveals Dynamics of the Phased Progression of Pluripotency

Research output: Contribution to journalJournal articleResearchpeer-review

Pengyi Yang, Sean J Humphrey, Senthilkumar Cinghu, Rajneesh Pathania, Andrew J Oldfield, Dhirendra Kumar, Dinuka Perera, Jean Y H Yang, David E James, Matthias Mann, Raja Jothi

Pluripotency is highly dynamic and progresses through a continuum of pluripotent stem cell states. The two states that bookend the pluripotency continuum, naive and primed, are well characterized, but our understanding of the intermediate states and transitions between them remains incomplete. Here, we dissect the dynamics of pluripotent state transitions underlying pre- to post-implantation epiblast differentiation. Through comprehensive mapping of the proteome, phosphoproteome, transcriptome, and epigenome of embryonic stem cells transitioning from naive to primed pluripotency, we find that rapid, acute, and widespread changes to the phosphoproteome precede ordered changes to the epigenome, transcriptome, and proteome. Reconstruction of the kinase-substrate networks reveals signaling cascades, dynamics, and crosstalk. Distinct waves of global proteomic changes mark discrete phases of pluripotency, with cell-state-specific surface markers tracking pluripotent state transitions. Our data provide new insights into multi-layered control of the phased progression of pluripotency and a foundation for modeling mechanisms regulating pluripotent state transitions (www.stemcellatlas.org).

Original languageEnglish
JournalCell Systems
Volume8
Issue number5
Pages (from-to)427-445.e10
ISSN2405-4712
DOIs
Publication statusPublished - 22 May 2019
Externally publishedYes

Bibliographical note

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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