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Multi-omic Profiling Reveals Dynamics of the Phased Progression of Pluripotency
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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 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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