Embryonic stem cell potency fluctuates with endogenous retrovirus activity

Todd S. Macfarlan, Wesley D. Gifford, Shawn Driscoll, Karen Lettieri, Helen M. Rowe, Dario Bonanomi, Amy Firth, Oded Singer, Didier Trono and Samuel L. Pfaff ()
Additional contact information
Todd S. Macfarlan: Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, California 92037, USA
Wesley D. Gifford: Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, California 92037, USA
Shawn Driscoll: Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, California 92037, USA
Karen Lettieri: Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, California 92037, USA
Helen M. Rowe: School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland
Dario Bonanomi: Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, California 92037, USA
Amy Firth: Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, California 92037, USA
Oded Singer: Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, California 92037, USA
Didier Trono: School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland
Samuel L. Pfaff: Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, California 92037, USA

Nature, 2012, vol. 487, issue 7405, 57-63

Abstract: Abstract Embryonic stem (ES) cells are derived from blastocyst-stage embryos and are thought to be functionally equivalent to the inner cell mass, which lacks the ability to produce all extraembryonic tissues. Here we identify a rare transient cell population within mouse ES and induced pluripotent stem (iPS) cell cultures that expresses high levels of transcripts found in two-cell (2C) embryos in which the blastomeres are totipotent. We genetically tagged these 2C-like ES cells and show that they lack the inner cell mass pluripotency proteins Oct4 (also known as Pou5f1), Sox2 and Nanog, and have acquired the ability to contribute to both embryonic and extraembryonic tissues. We show that nearly all ES cells cycle in and out of this privileged state, which is partially controlled by histone-modifying enzymes. Transcriptome sequencing and bioinformatic analyses showed that many 2C transcripts are initiated from long terminal repeats derived from endogenous retroviruses, suggesting this foreign sequence has helped to drive cell-fate regulation in placental mammals.

Date: 2012
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DOI: 10.1038/nature11244

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