RT Journal Article
T1 Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells.
A1 Klawitter, Sabine
A1 Fuchs, Nina V
A1 Upton, Kyle R
A1 Muñoz-Lopez, Martin
A1 Shukla, Ruchi
A1 Wang, Jichang
A1 Garcia-Cañadas, Marta
A1 Lopez-Ruiz, Cesar
A1 Gerhardt, Daniel J
A1 Sebe, Attila
A1 Grabundzija, Ivana
A1 Merkert, Sylvia
A1 Gerdes, Patricia
A1 Pulgarin, J Andres
A1 Bock, Anja
A1 Held, Ulrike
A1 Witthuhn, Anett
A1 Haase, Alexandra
A1 Sarkadi, Balázs
A1 Löwer, Johannes
A1 Wolvetang, Ernst J
A1 Martin, Ulrich
A1 Ivics, Zoltán
A1 Izsvák, Zsuzsanna
A1 Garcia-Perez, Jose L
A1 Faulkner, Geoffrey J
A1 Schumann, Gerald G
AB 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.
YR 2016
FD 2016-01-08
LK http://hdl.handle.net/10668/9713
UL http://hdl.handle.net/10668/9713
LA en
DS RISalud
RD Apr 19, 2025