title: Engineered LINE-1 retrotransposition in nondividing human neurons.
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.
authors.affiliation: Department of Genomic Medicine and Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Macia
authors.affiliation: Department of Genomic Medicine and Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Widmann
authors.affiliation: Department of Genomic Medicine and Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Heras
authors.affiliation: Department of Oncology, GENYO, Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.
authors.forename: Veronica
authors.initials: V
authors.lastname: Ayllon
authors.affiliation: Department of Genomic Medicine and Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Sanchez
authors.affiliation: Department of Genomic Medicine and Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.
authors.forename: Meriem
authors.initials: M
authors.lastname: Benkaddour-Boumzaouad
authors.affiliation: Department of Genomic Medicine and Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.
authors.forename: Martin
authors.initials: M
authors.lastname: Muñoz-Lopez
authors.affiliation: Department of Genomic Medicine and Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Rubio
authors.affiliation: Department of Genomic Medicine and Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.
authors.forename: Suyapa
authors.initials: S
authors.lastname: Amador-Cubero
authors.affiliation: Department of Genomic Medicine and Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Blanco-Jimenez
authors.affiliation: Unidad de Biotecnología Celular, ISCIII, Madrid, E-28021, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Garcia-Castro
authors.affiliation: Department of Oncology, GENYO, Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.|Josep Carreras Leukemia Research Institute, Department of Biomedicine, School of Medicine, University of Barcelona, Instituciò Catalana Recerca Estudis Avançats (ICREA), 08036 Barcelona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Menendez
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Ng
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Alysson R
authors.initials: AR
authors.lastname: Muotri
authors.affiliation: McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Goodier
authors.affiliation: Department of Genomic Medicine and Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016 Granada, Spain.|Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Garcia-Perez
mesh_terms: D002455:Cell Division; D002478:Cells, Cultured; D004251:DNA Transposable Elements; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009030:Mosaicism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements