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| Status |
Public on Aug 22, 2020 |
| Title |
Regulation of retrotransposon activity and telomeres in primed pluripotent stem cells (ChIP-seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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
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| Overall design |
We cultured naive and primed mESCs for fifteen passages under naïve and primed conditions to test their gene expression, telomere analysis, transposon elements transcription, genomic stability ,etc.
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| Contributor(s) |
Fu H, Zhang W, Li N, Liu L |
| Citation(s) |
34243810 |
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| Submission date |
Jul 15, 2020 |
| Last update date |
Jul 20, 2021 |
| Contact name |
Weiyu Zhang |
| E-mail(s) |
ch8316f5eyu@gmail.com
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| Phone |
18902012072
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| Organization name |
Nankai University
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| Street address |
No.38 Tongyan Road, Jinnan District
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| City |
Tainjin |
| ZIP/Postal code |
300350 |
| Country |
China |
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| Platforms (1) |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE140667 |
Regulation of retrotransposon activity and telomeres in primed pluripotent stem cells |
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| Relations |
| BioProject |
PRJNA646471 |
| SRA |
SRP272080 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE154487_RAW.tar |
9.6 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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