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

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
doi: https://doi.org/10.1101/415430
Pengyi Yang
Epigenetics & Stem Cell Biology Laboratory, NIEHS, NIH, USA; University of Sydney, Australia;
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Sean J Humphrey
Max Planck Institute of Biochemistry, Martinsried, Germany; University of Sydney, Australia;
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Senthilkumar Cinghu
Epigenetics & Stem Cell Biology Laboratory, NIEHS, NIH, USA;
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Rajneesh Pathania
Epigenetics & Stem Cell Biology Laboratory, NIEHS, NIH, USA;
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Andrew J Oldfield
Epigenetics & Stem Cell Biology Laboratory, NIEHS, NIH; Institute of Human Genetics, CNRS, France;
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Dhirendra Kumar
Epigenetics & Stem Cell Biology Laboratory, NIEHS, NIH, USA;
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Dinuka Perera
University of Sydney, Australia;
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Jean Y.H. Yang
University of Sydney, Australia;
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David E James
University of Sydney, Australia;
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Matthias Mann
Max Planck Institute of Biochemistry, Martinsried, Germany
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Raja Jothi
Epigenetics & Stem Cell Biology Laboratory, NIEHS, NIH, USA;
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  • For correspondence: jothi@mail.nih.gov
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Abstract

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 remain 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 mouse 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 kinase-substrate networks reveals signaling cascades, dynamics, and crosstalk. Distinct waves of global proteomic changes demarcate discrete phases of pluripotency, characterized by cell-state-specific surface marker expression. Our data provide new insights into the multi-layered control of the phased progression of pluripotency and a foundation for modeling mechanisms underlying pre- to post-implantation epiblast differentiation.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 19, 2018.
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Multi-Omic Profiling Reveals Dynamics of the Phased Progression of Pluripotency
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
bioRxiv 415430; doi: https://doi.org/10.1101/415430
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Multi-Omic Profiling Reveals Dynamics of the Phased Progression of Pluripotency
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
bioRxiv 415430; doi: https://doi.org/10.1101/415430

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