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dc.contributor.authorDella Valle, Francesco
dc.contributor.authorThimma, Manjula P
dc.contributor.authorCaiazzo, Massimiliano
dc.contributor.authorPulcrano, Salvatore
dc.contributor.authorCelii, Mirko
dc.contributor.authorAdroub, Sabir A
dc.contributor.authorLiu, Peng
dc.contributor.authorAlanis Lobato, Gregorio
dc.contributor.authorBroccoli, Vania
dc.contributor.authorOrlando, Valerio
dc.date.accessioned2020-01-20T05:48:49Z
dc.date.available2020-01-20T05:48:49Z
dc.date.issued2020-01-02
dc.identifier.citationDella Valle, F., Thimma, M. P., Caiazzo, M., Pulcrano, S., Celii, M., Adroub, S. A., … Orlando, V. (2020). Transdifferentiation of Mouse Embryonic Fibroblasts into Dopaminergic Neurons Reactivates LINE-1 Repetitive Elements. Stem Cell Reports, 14(1), 60–74. doi:10.1016/j.stemcr.2019.12.002
dc.identifier.doi10.1016/j.stemcr.2019.12.002
dc.identifier.urihttp://hdl.handle.net/10754/661096
dc.description.abstractIn mammals, LINE-1 (L1) retrotransposons constitute between 15% and 20% of the genome. Although only a few copies have retained the ability to retrotranspose, evidence in brain and differentiating pluripotent cells indicates that L1 retrotransposition occurs and creates mosaics in normal somatic tissues. The function of de novo insertions remains to be understood. The transdifferentiation of mouse embryonic fibroblasts to dopaminergic neuronal fate provides a suitable model for studying L1 dynamics in a defined genomic and unaltered epigenomic background. We found that L1 elements are specifically re-expressed and mobilized during the initial stages of reprogramming and that their insertions into specific acceptor loci coincides with higher chromatin accessibility and creation of new transcribed units. Those events accompany the maturation of neuronal committed cells. We conclude that L1 retrotransposition is a non-random process correlating with chromatin opening and lncRNA production that accompanies direct somatic cell reprogramming.
dc.description.sponsorshipWe are grateful to Fred Gage (Salk Institute) for the L1-EGFP Plasmid and stimulating discussions. John Goodier for pGF21 and pTN201 plasmids. Edith Heard for pTNC7 plasmid. V.O. is supported by King Abdullah University of Science and Technology (BAS 1037/01-01, CRG URF 126310101). M.C. is supported by Italian Ministry of University and Education grant MIUR FIR 2013 RBFR13LH4X_002. V.B. is supported by Italian Ministry of University and Education, Italian Institute of Technology Seed project, Telethon Foundation, Cariplo Foundation, and Michael Fox Foundation and ERC grant AdERC #340527. Thanks to Dr. Giancarlo Bellenchi for sharing reagents and laboratory facilities.
dc.publisherElsevier BV
dc.relation.urlhttps://linkinghub.elsevier.com/retrieve/pii/S2213671119304163
dc.relation.urlhttp://www.cell.com/article/S2213671119304163/pdf
dc.rightsThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/.
dc.titleTransdifferentiation of Mouse Embryonic Fibroblasts into Dopaminergic Neurons Reactivates LINE-1 Repetitive Elements.
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentComputer Science Program
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
dc.contributor.departmentEnvironmental Science and Engineering Program
dc.contributor.departmentKing Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, KAUST Environmental Epigenetics Program, Bld 2, Level 3, Room 3234, 4700 King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
dc.identifier.journalStem cell reports
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), 3584 Utrecht, the Netherlands
dc.contributor.institutionInstitute of Genetics and Biophysics,
dc.contributor.institutionDivision of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
dc.contributor.institutionInstitute of Molecular Biology, Computational Biology and Data Mining Unit, 55128 Mainz, Germany.
kaust.personDella Valle, Francesco
kaust.personThimma, Manjula P
kaust.personCelii, Mirko
kaust.personAdroub, Sabir A
kaust.personLiu, Peng
kaust.personAlanis Lobato, Gregorio
kaust.personOrlando, Valerio
refterms.dateFOA2020-01-20T05:50:06Z
dc.date.published-online2020-01-02
dc.date.published-print2020-01


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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).