TY - JOUR
T1 - Multi-omic Profiling Reveals Dynamics of the Phased Progression of Pluripotency
AU - Yang, Pengyi
AU - Humphrey, Sean J
AU - Cinghu, Senthilkumar
AU - Pathania, Rajneesh
AU - Oldfield, Andrew J
AU - Kumar, Dhirendra
AU - Perera, Dinuka
AU - Yang, Jean Y H
AU - James, David E
AU - Mann, Matthias
AU - Jothi, Raja
N1 - Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2019/5/22
Y1 - 2019/5/22
N2 - 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).
AB - 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).
U2 - 10.1016/j.cels.2019.03.012
DO - 10.1016/j.cels.2019.03.012
M3 - Journal article
C2 - 31078527
VL - 8
SP - 427-445.e10
JO - Cell Systems
JF - Cell Systems
SN - 2405-4712
IS - 5
ER -