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  Distinct transcription kinetics of pluripotent cell states

Shao, R., Kumar, B., Lidschreiber, K., Lidschreiber, M., Cramer, P., & Elsässer, S. J. (2022). Distinct transcription kinetics of pluripotent cell states. Molecular Systems Biology, 18(1): e10407. doi:10.15252/msb.202110407.

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Datensatz-Permalink: https://hdl.handle.net/21.11116/0000-0009-E255-8 Versions-Permalink: https://hdl.handle.net/21.11116/0000-000C-D5D3-5
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 Urheber:
Shao, R., Autor
Kumar, B., Autor
Lidschreiber, K.1, Autor           
Lidschreiber, M.1, Autor           
Cramer, P.1, Autor           
Elsässer, S. J., Autor
Affiliations:
1Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350224              

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Schlagwörter: mouse pluripotent stem cells; transcription termination; transcription unit annotation; transcription velocity; transient transcriptome sequencing
 Zusammenfassung: Mouse embryonic stem cells (mESCs) can adopt naïve, ground, and paused pluripotent states that give rise to unique transcriptomes. Here, we use transient transcriptome sequencing (TT-seq) to define both coding and non-coding transcription units (TUs) in these three pluripotent states and combine TT-seq with RNA polymerase II occupancy profiling to unravel the kinetics of RNA metabolism genome-wide. Compared to the naïve state (serum), RNA synthesis and turnover rates are globally reduced in the ground state (2i) and the paused state (mTORi). The global reduction in RNA synthesis goes along with a genome-wide decrease of polymerase elongation velocity, which is related to epigenomic features and alterations in the Pol II termination window. Our data suggest that transcription activity is the main determinant of steady state mRNA levels in the naïve state and that genome-wide changes in transcription kinetics invoke ground and paused pluripotent states.

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Sprache(n): eng - English
 Datum: 2022-01-122022
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.15252/msb.202110407
 Art des Abschluß: -

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Projektname : Bioinformatics analyses were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) at Uppmax server (projects SNIC 2020/15-9, SNIC 2020/6-3, uppstore2018208, SNIC 2018/3-669, sllstore2017057, SNIC 2017/1-508). We thank members of the Elsässer laboratory for comments and help with experiments and analysis. K.L., M.L., and P.C. were funded by CIMED and SciLifeLab. S.J.E. acknowledges funding by the Karolinska Institutet SFO for Molecular Biosciences, Vetenskapsrådet (2015-04815, 2020-04313), H2020 ERC Starting Grant (715024 RAPID), Åke Wibergs Stiftelse (M15-0275), Cancerfonden (2015/430). R.S. acknowledges funding from the Chinese Scholarship Council.
Grant ID : -
Förderprogramm : -
Förderorganisation : -
Projektname : RAPID
Grant ID : 715024
Förderprogramm : Horizon 2020 (H2020)
Förderorganisation : European Commission (EC)

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Titel: Molecular Systems Biology
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: London : Nature Pub. Group
Seiten: 19 Band / Heft: 18 (1) Artikelnummer: e10407 Start- / Endseite: - Identifikator: ISSN: 1744-4292
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000021290