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Engineered LINE-1 retrotransposition in nondividing human neurons

Authors :: Jose L. Garcia-Perez
Philip Ng
Alejandro Rubio
Laura Sánchez
Javier García-Castro
Sara R. Heras
John L. Goodier
Angela Macia
Eva Blanco-Jimenez
Martin Muñoz-Lopez
Alysson R. Muotri
Meriem Benkaddour-Boumzaouad
Thomas J. Widmann
Verónica Ayllón
Suyapa Amador-Cubero
Pablo Menendez
United States Department of Defense
National Institutes of Health (Estados Unidos)
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
European Research Council
Howard Hughes Medical Institute
Wellcome Trust
Unión Europea. Comisión Europea. 7 Programa Marco
Department of Defense USA
National Institutes of Health (United States)
European Regional Development Fund (ERDF/FEDER)
7º Programa Marco - Comisión Europea
Source :: Genome research, vol 27, iss 3, Digibug. Repositorio Institucional de la Universidad de Granada, Consejo Superior de Investigaciones Científicas (CSIC), Genome Research, r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol, instname, Digibug: Repositorio Institucional de la Universidad de Granada, Universidad de Granada (UGR), Repisalud, Instituto de Salud Carlos III (ISCIII), Macia, A, Widmann, T J, Heras, S R, Ayllon, V, Sanchez, L, Benkaddour-Boumzaouad, M, Muñoz-Lopez, M, Rubio, A, Amador-Cubero, S, Blanco-Jimenez, E, Garcia-Castro, J, Menendez, P, Ng, P, Muotri, A R, Goodier, J L & Garcia-Perez, J L 2017, ' Engineered LINE-1 retrotransposition in nondividing human neurons ', Genome Research, vol. 27, no. 3, pp. 335-348 . https://doi.org/10.1101/gr.206805.116
Publication Year :: 2016
Publisher :: Cold Spring Harbor Laboratory, 2016.
Abstract: Half the human genome is made of transposable elements (TEs), whose ongoing activity continues to impact our genome. LINE-1 (or L1) is an autonomous non-LTR retrotransposon in the human genome, comprising 17% of its genomic mass and containing an average of 80–100 active L1s per average genome that provide a source of inter-individual variation. New LINE-1 insertions are thought to accumulate mostly during human embryogenesis. Surprisingly, the activity of L1s can further impact the somatic human brain genome. However, it is currently unknown whether L1 can retrotranspose in other somatic healthy tissues or if L1 mobilization is restricted to neuronal precursor cells (NPCs) in the human brain. Here, we took advantage of an engineered L1 retrotransposition assay to analyze L1 mobilization rates in human mesenchymal (MSCs) and hematopoietic (HSCs) somatic stem cells. Notably, we have observed that L1 expression and engineered retrotransposition is much lower in both MSCs and HSCs when compared to NPCs. Remarkably, we have further demonstrated for the first time that engineered L1s can retrotranspose efficiently in mature nondividing neuronal cells. Thus, these findings suggest that the degree of somatic mosaicism and the impact of L1 retrotransposition in the human brain is likely much higher than previously thought. United States Department of Defense BC051386 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Neurological Disorders & Stroke (NINDS) 1R03NS087290-01 ALS Therapy Alliance 2013-F-067 Marie Curie IRG project FP7-PEOPLE-2007-4-3-IRG: SOMATIC LINE-1 European Research Council (ERC) ERC-STG-2012-233764 Howard Hughes Medical Institute IECS-55007420 Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund (ISFF2) Plan Nacional de I+D+I FIS-FEDER-PI11/01489 FIS-FEDER-PI14/02152 PCIN-2014-115-ERA-NET NEURON II CICE-FEDER-P09-CTS-4980 CICE-FEDER-P12-CTS-2256 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Neurological Disorders & Stroke (NINDS) R03NS087290 ICREA