Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Klawitter, Sabine ; Fuchs, Nina V ; Upton, Kyle R ; Muñoz-Lopez, Martin ; Shukla, Ruchi ; Wang, Jichang ; Garcia-Cañadas, Marta ; Lopez-Ruiz, Cesar ; Gerhardt, Daniel J and Sebe, Attila , et al. (2016) In Nature Communications 7. p.1-14
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alu Elements/genetics, Calcium-Binding Proteins/genetics, Cell Line, Cell Proliferation/genetics, Cellular Reprogramming/genetics, Cellular Reprogramming Techniques, Embryonic Stem Cells/metabolism, Epigenesis, Genetic, Humans, Induced Pluripotent Stem Cells/metabolism, Long Interspersed Nucleotide Elements/genetics, Minisatellite Repeats, Retroelements/genetics, Vesicular Transport Proteins/genetics
in
Nature Communications
volume
7
article number
10286
pages
1 - 14
publisher
Nature Publishing Group
external identifiers
  • pmid:26743714
  • scopus:84953911769
ISSN
2041-1723
DOI
10.1038/ncomms10286
language
English
LU publication?
no
id
1ec6aca0-4671-4636-8824-60492b4194d6
date added to LUP
2024-06-10 16:18:19
date last changed
2024-06-12 03:06:28
@article{1ec6aca0-4671-4636-8824-60492b4194d6,
  abstract     = {{<p>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.</p>}},
  author       = {{Klawitter, Sabine and Fuchs, Nina V and Upton, Kyle R and Muñoz-Lopez, Martin and Shukla, Ruchi and Wang, Jichang and Garcia-Cañadas, Marta and Lopez-Ruiz, Cesar and Gerhardt, Daniel J and Sebe, Attila and Grabundzija, Ivana and Merkert, Sylvia and Gerdes, Patricia and Pulgarin, J Andres and Bock, Anja and Held, Ulrike and Witthuhn, Anett and Haase, Alexandra and Sarkadi, Balázs and Löwer, Johannes and Wolvetang, Ernst J and Martin, Ulrich and Ivics, Zoltán and Izsvák, Zsuzsanna and Garcia-Perez, Jose L and Faulkner, Geoffrey J and Schumann, Gerald G}},
  issn         = {{2041-1723}},
  keywords     = {{Alu Elements/genetics; Calcium-Binding Proteins/genetics; Cell Line; Cell Proliferation/genetics; Cellular Reprogramming/genetics; Cellular Reprogramming Techniques; Embryonic Stem Cells/metabolism; Epigenesis, Genetic; Humans; Induced Pluripotent Stem Cells/metabolism; Long Interspersed Nucleotide Elements/genetics; Minisatellite Repeats; Retroelements/genetics; Vesicular Transport Proteins/genetics}},
  language     = {{eng}},
  month        = {{01}},
  pages        = {{1--14}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells}},
  url          = {{http://dx.doi.org/10.1038/ncomms10286}},
  doi          = {{10.1038/ncomms10286}},
  volume       = {{7}},
  year         = {{2016}},
}