Regulation of retrotransposon activity and telomeres in primed pluripotent stem cells
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PROVIDER: PRJNA590478 | ENA |
REPOSITORIES: ENA
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Project description:Regulation of retrotransposon activity and telomeres in primed pluripotent stem cells (ChIP-seq)
| PRJNA646471 | ENA
Project description:Regulation of retrotransposon activity and telomeres in primed pluripotent stem cells (RNA-seq)
| PRJNA590484 | ENA
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
2020-08-22 | GSE154487 | GEO
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
2020-08-22 | GSE140665 | GEO
Project description:Telomeres suppress the activity of retrotransposons in pluripotent stem cells
| PRJNA484115 | ENA
Project description:Telomeres suppress the activity of retrotransposons in pluripotent stem cells [exp2]
| PRJNA484113 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-08-23 | GSE140667 | GEO
Project description:BackgroundNaïve and primed pluripotent stem cells (PSCs) represent two different pluripotent states. Primed PSCs following in vitro culture exhibit lower developmental potency as evidenced by failure in germline chimera assays, unlike mouse naïve PSCs. However, the molecular mechanisms underlying the lower developmental competency of primed PSCs remain elusive.ResultsWe examine the regulation of telomere maintenance, retrotransposon activity, and genomic stability of primed PSCs and compare them with naïve PSCs. Surprisingly, primed PSCs only minimally maintain telomeres and show fragile telomeres, associated with declined DNA recombination and repair activity, in contrast to naïve PSCs that robustly elongate telomeres. Also, we identify LINE1 family integrant L1Md_T as naïve-specific retrotransposon and ERVK family integrant IAPEz to define primed PSCs, and their transcription is differentially regulated by heterochromatic histones and Dnmt3b. Notably, genomic instability of primed PSCs is increased, in association with aberrant retrotransposon activity.ConclusionsOur data suggest that fragile telomere, retrotransposon-associated genomic instability, and declined DNA recombination repair, together with reduced function of cell cycle and mitochondria, increased apoptosis, and differentiation properties may link to compromised developmental potency of primed PSCs, noticeably distinguishable from naïve PSCs.
| S-EPMC8268579 | biostudies-literature
Project description:Naive and primed human pluripotent stem cells (hPSC) provide valuable models to study cellular and molecular developmental processes. The lack of detailed information about cell-surface protein expression in these two pluripotent cell types prevents an understanding of how the cells communicate and interact with their microenvironments. Here, we used plasma membrane profiling to directly measure cell-surface protein expression in naive and primed hPSC. This unbiased approach quantified over 1700 plasma membrane proteins including those involved in cell adhesion, signalling and cell interactions. Notably, multiple cytokine receptors upstream of JAK-STAT signalling were more abundant in naive hPSC. In addition, functional experiments showed that FOLR1 and SUSD2 proteins are highly expressed at the cell surface in naive hPSC but are not required to establish human naive pluripotency. This study provides a comprehensive stem cell proteomic resource that uncovers differences in signalling pathway activity and has identified new markers to define human pluripotent states.
2020-04-17 | PXD015359 | Pride
Project description:Here we analyse transcriptome profiles of naive, primed and intermediate populations of human pluripotent stem cells
2017-03-23 | GSE93241 | GEO