Dataset Information

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

ABSTRACT: Pluripotency is highly dynamic and progresses through a continuum of pluripotent stem-cell states. The two states that bookend the pluripotency continuum, naïve 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 embryonic stem cells transitioning from naïve 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 mark discrete phases of pluripotency, with cell state-specific surface markers tracking pluripotent state transitions. Our data provide new insights into the multi-layered control of the phased progression of pluripotency and a foundation for modeling mechanisms regulating pluripotent state transitions (www.stemcellatlasorg).

OTHER RELATED OMICS DATASETS IN: GSE117896

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryo, Stem Cell

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD010621 | Pride | 2019-05-07

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20150726_QEp2_LC10_SeHu_SA_mESC_EasyPhos_A1.raw	Raw
	20150726_QEp2_LC10_SeHu_SA_mESC_EasyPhos_A10.raw	Raw
	20150726_QEp2_LC10_SeHu_SA_mESC_EasyPhos_A11.raw	Raw
	20150726_QEp2_LC10_SeHu_SA_mESC_EasyPhos_A12.raw	Raw
	20150726_QEp2_LC10_SeHu_SA_mESC_EasyPhos_A2.raw	Raw

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Publications

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

Yang Pengyi P Humphrey Sean J SJ Cinghu Senthilkumar S Pathania Rajneesh R Oldfield Andrew J AJ Kumar Dhirendra D Perera Dinuka D Yang Jean Y H JYH James David E DE Mann Matthias M Jothi Raja R

Cell systems 20190508 5

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, ...[more]

PMID: 31078527

Similar Datasets

Project description:Naïve and primed pluripotent states represent two different states of pluripotency. Mouse naïve pluripotent stem cells (PSCs) exhibit germline competence as determined by chimera production test and can generate all-PSC mice by tetraploid embryo complementation (TEC) test, the most stringent functional test of developmental potency. By contrast, primed PSCs fail in germline chimeras and TEC test. Unfortunately, these tests cannot be applied to characterization of developmental pluripotency of human PSCs due to ethic issue. Extensive studies demonstrated that naïve and primed pluripotent state exhibits clear epigenome differences. Here we uncover surprising differences in telomere maintenance, retrotransposon activity and genomic stability between these two pluripotent states. Although both states express high telomerase activity, naïve PSCs show robust telomere elongation capacity, associated with higher telomere recombination, consistent with sporadic expression of two-cell (2C) genes including Zscan4. Distinctively, primed PSCs only can maintain their telomere length but without elongation, in association with repression of 2C genes, and increased telomere fragility and telomeric DNA damage with passages. RNA-seq revealed that DNA repair and especially recombination repair pathways are down-regulated in primed state compared to naïve state cells, corroborating the robust DNA repair capacity and genome stability in naïve PSCs. These data suggest that vigorous telomere elongation of naïve state may act to minimize DNA damage to the genome. Furthermore, we identified LINE1 family integrant L1Md_T as naïve-specific retrotransposon and ERVK family integrant IAPEz-int to define primed PSCs, distinguishing the two pluripotent states. Heterochromatin modifications and Dnmt3b differentially regulate transcription of the 2C genes and retrotransposons. Notably, aberrant expression of retrotransposons links to increased genomic stability of primed PSCs. Hence, our data reveals that telomere regulation and retrotransposon activity markedly distinguishes naïve from primed pluripotent state. These new criteria may facilitate induction of high quality and additional characterization of developmental pluripotency and scrutinizing the genomic stability of human naïve PSCs for regenerative medicine