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

Research output: Contribution to journalArticle

  • Sabine Klawitter
  • Nina V Fuchs
  • Kyle R Upton
  • Martin Muñoz-Lopez
  • Ruchi Shukla
  • Jichang Wang
  • Marta Garcia-Cañadas
  • Cesar Lopez-Ruiz
  • Daniel J Gerhardt
  • Attila Sebe
  • Ivana Grabundzija
  • Sylvia Merkert
  • Patricia Gerdes
  • J Andres Pulgarin
  • Anja Bock
  • Ulrike Held
  • Anett Witthuhn
  • Alexandra Haase
  • Balázs Sarkadi
  • Johannes Löwer
  • Ernst J Wolvetang
  • Ulrich Martin
  • Zoltán Ivics
  • Zsuzsanna Izsvák
  • Geoffrey J Faulkner
  • Gerald G Schumann

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    Rights statement: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Original languageEnglish
Pages (from-to)10286
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 8 Jan 2016

Abstract

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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