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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BibTeX (Download)
@article{Klawitter2016-ur,
title = {Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells},
author = {Sabine Klawitter and Nina V Fuchs and Kyle R Upton and Martin Mu{~n}oz-Lopez and Ruchi Shukla and Jichang Wang and Marta Garcia-Ca{~n}adas and Cesar Lopez-Ruiz and Daniel J Gerhardt and Attila Sebe and Ivana Grabundzija and Sylvia Merkert and Patricia Gerdes and Andres J Pulgarin and Anja Bock and Ulrike Held and Anett Witthuhn and Alexandra Haase and Bal\'{a}zs Sarkadi and Johannes L\"{o}wer and Ernst J Wolvetang and Ulrich Martin and Zolt\'{a}n Ivics and Zsuzsanna Izsv\'{a}k and Jose L Garcia-Perez and Geoffrey J Faulkner and Gerald G Schumann},
url = {http://dx.doi.org/10.1038/ncomms10286},
year = {2016},
date = {2016-01-01},
journal = {Nat. Commun.},
volume = {7},
pages = {10286},
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.},
keywords = {Faulknerlab, Faulknerlab;TEBreak paper, Major_Publication},
pubstate = {published},
tppubtype = {article}
}