Format

Send to

Choose Destination
Nature. 2014 Dec 18;516(7531):405-9. doi: 10.1038/nature13804. Epub 2014 Oct 15.

Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.

Author information

1
Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
2
1] Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany [2] Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, 320 Yueyang Road, Shanghai 200031, China.
3
University of Bath, Department of Biology and Biochemistry, Bath, Somerset BA2 7AY, UK.
4
1] Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany [2] Paul-Ehrlich-Institute, Division of Medical Biotechnology, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany.
5
Paul-Ehrlich-Institute, Division of Medical Biotechnology, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany.
6
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.

Abstract

Naive embryonic stem cells hold great promise for research and therapeutics as they have broad and robust developmental potential. While such cells are readily derived from mouse blastocysts it has not been possible to isolate human equivalents easily, although human naive-like cells have been artificially generated (rather than extracted) by coercion of human primed embryonic stem cells by modifying culture conditions or through transgenic modification. Here we show that a sub-population within cultures of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) manifests key properties of naive state cells. These naive-like cells can be genetically tagged, and are associated with elevated transcription of HERVH, a primate-specific endogenous retrovirus. HERVH elements provide functional binding sites for a combination of naive pluripotency transcription factors, including LBP9, recently recognized as relevant to naivety in mice. LBP9-HERVH drives hESC-specific alternative and chimaeric transcripts, including pluripotency-modulating long non-coding RNAs. Disruption of LBP9, HERVH and HERVH-derived transcripts compromises self-renewal. These observations define HERVH expression as a hallmark of naive-like hESCs, and establish novel primate-specific transcriptional circuitry regulating pluripotency.

PMID:
25317556
DOI:
10.1038/nature13804
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center