Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance

Alexandre Fort, Kosuke Hashimoto, Daisuke Yamada, Md Salimullah, Chaman A. Keya, Alka Saxena, Alessandro Bonetti, Irina Voineagu, Nicolas Bertin, Anton Kratz, Yukihiko Noro, Chee Hong Wong, Michiel De Hoon, Robin Andersson, Albin Sandelin, Harukazu Suzuki, Chia Lin Wei, Haruhiko Koseki, Yuki Hasegawa, Alistair R.R. ForrestPiero Carninci*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

221 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)558-566
Number of pages9
JournalNature Genetics
Issue number6
StatePublished - Jun 2014
Externally publishedYes

Bibliographical note

Funding Information:
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.

ASJC Scopus subject areas

  • Genetics


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