Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells
| Autor: | Gerald G. Schumann, Zoltán Ivics, Marta García-Cañadas, Ulrike Held, Zsuzsanna Izsvák, Anett Witthuhn, Ruchi Shukla, Ernst J. Wolvetang, Daniel J. Gerhardt, Balázs Sarkadi, J. Andres Pulgarin, Johannes Löwer, Sabine Klawitter, Jose L. Garcia-Perez, Alexandra Haase, Ulrich Martin, Sylvia Merkert, Martin Muñoz-Lopez, Attila Sebe, Anja Bock, Ivana Grabundzija, Kyle R. Upton, Jichang Wang, Patricia Gerdes, Cesar Lopez-Ruiz, Nina V. Fuchs, Geoffrey J. Faulkner |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
endocrine system Retroelements Science Induced Pluripotent Stem Cells Vesicular Transport Proteins General Physics and Astronomy Alu element Retrotransposon Germ layer Minisatellite Repeats Biology General Biochemistry Genetics and Molecular Biology Article Cell Line Epigenesis Genetic 03 medical and health sciences Alu Elements Humans Cellular Reprogramming Techniques Epigenetics Induced pluripotent stem cell Author Correction Embryonic Stem Cells Cell Proliferation Genetics Multidisciplinary Calcium-Binding Proteins General Chemistry Cellular Reprogramming Embryonic stem cell Cell biology 030104 developmental biology Long Interspersed Nucleotide Elements Cardiovascular and Metabolic Diseases Reprogramming |
| Zdroj: | Nature Communications Klawitter, S, Fuchs, N V, Upton, K R, Muñoz-Lopez, M, Shukla, R, Wang, J, Garcia-Cañadas, M, Lopez-Ruiz, C, Gerhardt, D J, Sebe, A, Grabundzija, I, Merkert, S, Gerdes, P, Pulgarin, J A, Bock, A, Held, U, Witthuhn, A, Haase, A, Sarkadi, B, Löwer, J, Wolvetang, E J, Martin, U, Ivics, Z, Izsvák, Z, Garcia-Perez, J L, Faulkner, G J & Schumann, G G 2016, ' Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells ', Nature Communications, vol. 7, pp. 10286 . https://doi.org/10.1038/ncomms10286 Nature Communications, Vol 7, Iss 1, Pp 1-14 (2016) |
| ISSN: | 2041-1723 |
| Popis: | 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. Genetic and epigenetic abnormalities have been found to result from reprogramming of differentiated cells into human induced pluripotent stem cells (hiPSCs). Here, Klawitter et al. identify endogenous L1, Alu and SVA mobilization during reprogramming, highlighting the risk of insertional mutagens in hiPSCs. |
| Databáze: | OpenAIRE |
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