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Multi-omic Profiling Reveals Dynamics of the Phased Progression of Pluripotency
Open accessPublished version of a preprint
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 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).
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Metadata
- Authors
- Yang, P., Humphrey, S. J., Cinghu, S., Pathania, R., Oldfield, A. J., Kumar, D., Perera, D., Yang, J. Y. H., James, D. E., Mann, M., & Jothi, R.
- Affiliations
- The University of Sydney (AU)
- National Institutes of Health (US)
- Max Planck Institute of Biochemistry (DE)
- Corresponding author
- Yang, Pengyi
- Humphrey, Sean J.
- Jothi, Raja
- ORCID
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 8
- Issue
- 5
- Pages
- 427-445.e10
- ISSN
- 2405-4712 (ISSN-L)
- PMC
- PMC6544180
- OpenAlex
- W2950402574
- Cited by
- 146
- References
- 109
- Citations by year
- 2026: 6 · 2025: 21 · 2024: 14 · 2023: 28 · 2022: 25 · 2021: 26 · 2020: 20 · 2019: 6
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Systems (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg
- Australian Research Council
- National Institutes of Health
- European Molecular Biology Organization
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- pluripotency, naive pluripotency, primed pluripotency, embryonic stem cells, phosphoproteome, proteome, transcriptome, epigenome, signaling pathways
- MeSH terms
- Epigenome, Animals, Cell Differentiation, Germ Layers, Humans, Signal Transduction, Gene Expression Regulation, Developmental, Cell Lineage, Proteome, Pluripotent Stem Cells, Embryonic Stem Cells, Transcriptome
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