Klawitter, SabineFuchs, Nina VUpton, Kyle RMuñoz-Lopez, MartinShukla, RuchiWang, JichangGarcia-Cañadas, MartaLopez-Ruiz, CesarGerhardt, Daniel JSebe, AttilaGrabundzija, IvanaMerkert, SylviaGerdes, PatriciaPulgarin, J AndresBock, AnjaHeld, UlrikeWitthuhn, AnettHaase, AlexandraSarkadi, BalázsLöwer, JohannesWolvetang, Ernst JMartin, UlrichIvics, ZoltánIzsvák, ZsuzsannaGarcia-Perez, Jose LFaulkner, Geoffrey JSchumann, Gerald G2023-01-252023-01-252016-01-08http://hdl.handle.net/10668/9713Human 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Alu ElementsCalcium-Binding ProteinsCell LineCell ProliferationCellular ReprogrammingCellular Reprogramming TechniquesEmbryonic Stem CellsEpigenesis, GeneticHumansInduced Pluripotent Stem CellsLong Interspersed Nucleotide ElementsMinisatellite RepeatsRetroelementsVesicular Transport Proteinsresearch article26743714open access10.1038/ncomms102862041-1723PMC4729875https://www.nature.com/articles/ncomms10286.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729875/pdf