Abstract

The importance of microRNAs and long noncoding RNAs in the regulation of pluripotency has been documented; however, the noncoding components of stem cell gene networks remain largely unknown. Here we investigate the role of noncoding RNAs in the pluripotent state, with particular emphasis on nuclear and retrotransposon-derived transcripts. We have performed deep profiling of the nuclear and cytoplasmic transcriptomes of human and mouse stem cells, identifying a class of previously undetected stem cell–specific transcripts. We show that long terminal repeat (LTR)-derived transcripts contribute extensively to the complexity of the stem cell nuclear transcriptome. Some LTR-derived transcripts are associated with enhancer regions and are likely to be involved in the maintenance of pluripotency.

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Acknowledgements

The authors thank the RIKEN GeNAS sequencing platform for sequencing of the libraries. This work was supported by a grant to P.C. from the Japan Society for the Promotion of Science (JSPS) through the Funding Program for Next-Generation World-Leading Researchers (NEXT) initiated by the Council for Science and Technology Policy (CSTP), by a grand-in-aid for scientific research from JSPS to P.C. and A.F., and by a research grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) to the RIKEN Center for Life Science Technologies. FANTOM5 was made possible by a research grant for the RIKEN Omics Science Center from MEXT Japan to Y. Hayashizaki and by a grant for Innovative Cell Biology by Innovative Technology (Cell Innovation Program) from MEXT to Y. Hayashizaki. A.F. was supported by a JSPS long-term fellowship (P10782) and by a Swiss National Science Foundation Fellowship for Advanced Researchers (PA00P3_142122). K.H. was supported by European Union Framework Programme 7 (MODHEP project) for P.C. A.B. was supported by the Sigrid Juselius Foundation Fellowship. D.Y. and H.K. were supported by the Japan Science and Technology Agency CREST. R.A. and A. Sandelin were supported by funds from FP7/2007-2013/ERC grant agreement 204135, the Novo Nordisk Foundation, the Lundbeck Foundation and the Danish Cancer Society.

Author information

Author notes

    • Alka Saxena
    • , Irina Voineagu
    •  & Nicolas Bertin

    Present addresses: National Institute for Health Research, Biomedical Research Centre, Genomics Core Facility, Guy's Hospital, London, UK (A. Saxena), School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia (I.V.), and Cancer Science Institute of Singapore, National University of Singapore, Singapore (N.B.).

    • Alexandre Fort
    •  & Kosuke Hashimoto

    These authors contributed equally to this work.

Affiliations

  1. Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.

    • Alexandre Fort
    • , Kosuke Hashimoto
    • , Md Salimullah
    • , Chaman A Keya
    • , Alka Saxena
    • , Alessandro Bonetti
    • , Irina Voineagu
    • , Nicolas Bertin
    • , Anton Kratz
    • , Yukihiko Noro
    • , Michiel de Hoon
    • , Harukazu Suzuki
    • , Yuki Hasegawa
    • , Alistair R R Forrest
    •  & Piero Carninci
  2. Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

    • Daisuke Yamada
    •  & Haruhiko Koseki
  3. Sequencing Technology Group, Joint Genome Institute, Lawrence Berkeley National Laboratory, Walnut Creek, California, USA.

    • Chee-Hong Wong
    •  & Chia-Lin Wei
  4. Bioinformatics Centre, Department of Biology and Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.

    • Robin Andersson
    •  & Albin Sandelin

Consortia

  1. The FANTOM Consortium

    A full list of members and affiliations appear in the Supplementary Note.

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Contributions

P.C. led the project and oversaw the analyses. P.C., Y.H. and A.R.R.F. contributed to the design of the study. A.F., D.Y., M.S., C.A.K., A. Saxena, A.B., H.S., H.K., Y.N. and Y.H. contributed to data generation. A.F., K.H., I.V., N.B., M.d.H., A.R.R.F., A.K., R.A. and A. Sandelin contributed to data processing and analyses. C.-H.W. and C.-L.W. produced and analyzed ChIA-PET data. A.F., A.B., A.R.R.F. and P.C. wrote the manuscript with input from all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Piero Carninci.

Integrated supplementary information

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–11 and Supplementary Tables 1–5

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    Supplementary Data Set 1

    Human stem cell transcriptome profiling data sets.

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    Mouse stem cell transcriptome profiling data sets.

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DOI

https://doi.org/10.1038/ng.2965

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