title: Loss of transcriptional control over endogenous retroelements during reprogramming to pluripotency.
abstract: Endogenous retroelements (EREs) account for about half of the mouse or human genome, and their potential as insertional mutagens and transcriptional perturbators is suppressed by early embryonic epigenetic silencing. Here, we asked how ERE control is maintained during the generation of induced pluripotent stem cells (iPSCs), as this procedure involves profound epigenetic remodeling. We found that all EREs tested were markedly up-regulated during the reprogramming of either mouse embryonic fibroblasts, human CD34(+) cells, or human primary hepatocytes. At the iPSC stage, EREs of some classes were repressed, whereas others remained highly expressed, yielding a pattern somewhat reminiscent of that recorded in embryonic stem cells. However, variability persisted between individual iPSC clones in the control of specific ERE integrants. Both during reprogramming and in iPS cells, the up-regulation of specific EREs significantly impacted on the transcription of nearby cellular genes. While transcription triggered by specific ERE integrants at highly precise developmental stages may be an essential step toward obtaining pluripotent cells, the broad and unspecific unleashing of the repetitive genome observed here may contribute to the inefficiency of the reprogramming process and to the phenotypic heterogeneity of iPSCs.
authors.affiliation: School of Life Sciences and "Frontiers in Genetics" National Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Marc
authors.initials: M
authors.lastname: Friedli
authors.affiliation: School of Life Sciences and "Frontiers in Genetics" National Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Priscilla
authors.initials: P
authors.lastname: Turelli
authors.affiliation: School of Life Sciences and "Frontiers in Genetics" National Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Adamandia
authors.initials: A
authors.lastname: Kapopoulou
authors.affiliation: School of Life Sciences and "Frontiers in Genetics" National Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rauwel
authors.affiliation: School of Life Sciences and "Frontiers in Genetics" National Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Nathaly
authors.initials: N
authors.lastname: Castro-Díaz
authors.affiliation: School of Life Sciences and "Frontiers in Genetics" National Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Helen M
authors.initials: HM
authors.lastname: Rowe
authors.affiliation: School of Life Sciences and "Frontiers in Genetics" National Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ecco
authors.affiliation: Pediatric Surgery Laboratory, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland;
authors.forename: Carmen
authors.initials: C
authors.lastname: Unzu
authors.affiliation: School of Life Sciences and "Frontiers in Genetics" National Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Evarist
authors.initials: E
authors.lastname: Planet
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy and Vita Salute San Raffaele University, 20132 Milan, Italy;
authors.forename: Angelo
authors.initials: A
authors.lastname: Lombardo
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Bastien
authors.initials: B
authors.lastname: Mangeat
authors.affiliation: Pediatric Surgery Laboratory, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland;
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Wildhaber
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy and Vita Salute San Raffaele University, 20132 Milan, Italy;
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldini
authors.affiliation: School of Life Sciences and "Frontiers in Genetics" National Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland; didier.trono@epfl.ch.
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D020077:Endogenous Retroviruses / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D051379:Mice; D059467:Transcriptome; D015854:Up-Regulation