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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: e10407. doi:10.15252/msb.202110407.

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 Creators:
Shao, R., Author
Kumar, B., Author
Lidschreiber, K.1, Author              
Lidschreiber, M.1, Author              
Cramer, P.1, Author              
Elsässer, S. J., Author
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1Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350224              

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Free keywords: mouse pluripotent stem cells; transcription termination; transcription unit annotation; transcription velocity; transient transcriptome sequencing
 Abstract: 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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Language(s): eng - English
 Dates: 2022-01-12
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.15252/msb.202110407
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Title: Molecular Systems Biology
Source Genre: Journal
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Pages: 19 Volume / Issue: 18 Sequence Number: e10407 Start / End Page: - Identifier: -