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. Forrest; Piero Carninci

doi:10.1038/ng.2965

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 journal › Article › peer-review

223 Scopus citations

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.

Original language	English (US)
Pages (from-to)	558-566
Number of pages	9
Journal	Nature Genetics
Volume	46
Issue number	6
DOIs	https://doi.org/10.1038/ng.2965
State	Published - Jun 2014
Externally published	Yes

ASJC Scopus subject areas

Genetics

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Fort, A., Hashimoto, K., Yamada, D., Salimullah, M., Keya, C. A., Saxena, A., Bonetti, A., Voineagu, I., Bertin, N., Kratz, A., Noro, Y., Wong, C. H., De Hoon, M., Andersson, R., Sandelin, A., Suzuki, H., Wei, C. L., Koseki, H., Hasegawa, Y., ... Carninci, P. (2014). Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance. Nature Genetics, 46(6), 558-566. https://doi.org/10.1038/ng.2965

@article{0fa81fe251a14e7ab1c0c497ecb1ca83,

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

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.",

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

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.",

year = "2014",

month = jun,

doi = "10.1038/ng.2965",

language = "English (US)",

volume = "46",

pages = "558--566",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "6",

}

Fort, A, Hashimoto, K, Yamada, D, Salimullah, M, Keya, CA, Saxena, A, Bonetti, A, Voineagu, I, Bertin, N, Kratz, A, Noro, Y, Wong, CH, De Hoon, M, Andersson, R, Sandelin, A, Suzuki, H, Wei, CL, Koseki, H, Hasegawa, Y, Forrest, ARR & Carninci, P 2014, 'Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance', Nature Genetics, vol. 46, no. 6, pp. 558-566. https://doi.org/10.1038/ng.2965

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T1 - Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance

AU - Fort, Alexandre

AU - Hashimoto, Kosuke

AU - Yamada, Daisuke

AU - Salimullah, Md

AU - Keya, Chaman A.

AU - Saxena, Alka

AU - Bonetti, Alessandro

AU - Voineagu, Irina

AU - Bertin, Nicolas

AU - Kratz, Anton

AU - Noro, Yukihiko

AU - Wong, Chee Hong

AU - De Hoon, Michiel

AU - Andersson, Robin

AU - Sandelin, Albin

AU - Suzuki, Harukazu

AU - Wei, Chia Lin

AU - Koseki, Haruhiko

AU - Hasegawa, Yuki

AU - Forrest, Alistair R.R.

AU - Carninci, Piero

N1 - 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.

PY - 2014/6

Y1 - 2014/6

N2 - 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.

AB - 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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EP - 566

JO - Nature Genetics

JF - Nature Genetics

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ER -

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

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