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Nat Commun. 2016 Jan 8;7:10286. doi: 10.1038/ncomms10286.

Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells.

Author information

Division of Medical Biotechnology, Paul-Ehrlich-Institute, D-63225 Langen, Germany.
Max-Delbrück-Center for Molecular Medicine, D-13125 Berlin, Germany.
Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, Brisbane, Queensland 4102, Australia.
Department of Human DNA Variability, Pfizer/University of Granada and Andalusian Regional Government Center for Genomics and Oncology (GENYO), PTS Granada, 18016 Granada, Spain.
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiac, Thoracic, Transplantation, and Vascular Surgery; REBIRTH, Cluster of Excellence, Hannover Medical School, D-30625 Hannover, Germany.
Department of Biophysics and Radiation Biology, Semmelweis University, H-1094 Budapest, Hungary.
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Queensland 4072, Australia.
Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4072, Australia.


Human induced pluripotent stem cells (hiPSCs) are capable of unlimited proliferation and can differentiate in vitro to generate derivatives of the three primary germ layers. Genetic and epigenetic abnormalities have been reported by Wissing and colleagues to occur during hiPSC derivation, including mobilization of engineered LINE-1 (L1) retrotransposons. However, incidence and functional impact of endogenous retrotransposition in hiPSCs are yet to be established. Here we apply retrotransposon capture sequencing to eight hiPSC lines and three human embryonic stem cell (hESC) lines, revealing endogenous L1, Alu and SINE-VNTR-Alu (SVA) mobilization during reprogramming and pluripotent stem cell cultivation. Surprisingly, 4/7 de novo L1 insertions are full length and 6/11 retrotransposition events occurred in protein-coding genes expressed in pluripotent stem cells. We further demonstrate that an intronic L1 insertion in the CADPS2 gene is acquired during hiPSC cultivation and disrupts CADPS2 expression. These experiments elucidate endogenous retrotransposition, and its potential consequences, in hiPSCs and hESCs.

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