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

Official URL:https://doi.org/10.1038/nature13804
PubMed:View item in PubMed
Creators Name:Wang, J. and Xie, G. and Singh, M. and Ghanbarian, A.T. and Rasko, T. and Szvetnik, A. and Cai, H. and Besser, D. and Prigione, A. and Fuchs, N.V. and Schumann, G.G. and Chen, W. and Lorincz, M.C. and Ivics, Z. and Hurst, L.D. and Izsvak, Z.
Journal Title:Nature
Journal Abbreviation:Nature
Volume:516
Number:7531
Page Range:405-409
Date:18 December 2014
Keywords:Cultured Cells, DNA Transposable Elements, Embryonic Stem Cells, Endogenous Retroviruses, Gene Expression Profiling, Genetic Markers, Induced Pluripotent Stem Cells, Long Noncoding RNA, Transcription Factors
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.
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Item Type:Article

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