Long interspersed nuclear elements safeguard neural progenitors from precocious differentiation

Tomohisa Toda; Tracy A Bedrosian; Simon T Schafer; Michael S Cuoco; Sara B Linker; Saeed Ghassemzadeh; Lisa Mitchell; Jack T Whiteley; Nicole Novaresi; Aidan H McDonald; Iryna S Gallina; Hyojung Yoon; Mark E Hester; Monique Pena; Christina Lim; Emelia Suljic; Abed AlFatah Mansour; Matthieu Boulard; Sarah L Parylak; Fred H Gage

doi:10.1016/j.celrep.2024.113774

Long interspersed nuclear elements safeguard neural progenitors from precocious differentiation

Cell Rep. 2024 Feb 27;43(2):113774. doi: 10.1016/j.celrep.2024.113774. Epub 2024 Feb 13.

Authors

Tomohisa Toda¹, Tracy A Bedrosian², Simon T Schafer³, Michael S Cuoco⁴, Sara B Linker⁵, Saeed Ghassemzadeh⁵, Lisa Mitchell⁵, Jack T Whiteley⁵, Nicole Novaresi⁵, Aidan H McDonald⁵, Iryna S Gallina⁵, Hyojung Yoon⁶, Mark E Hester⁶, Monique Pena³, Christina Lim⁵, Emelia Suljic⁵, Abed AlFatah Mansour⁵, Matthieu Boulard⁷, Sarah L Parylak⁵, Fred H Gage⁸

Affiliations

¹ Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Laboratory of Neural Epigenomics, Institute of Medical Physics and Micro-tissue Engineering, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany; Nuclear Architecture in Neural Plasticity and Aging Laboratory, German Center for Neurodegenerative Diseases, 01307 Dresden, Germany. Electronic address: tomohisa.toda@fau.de.
² Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43205, USA.
³ Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich, Munich, Germany; TUM Center for Organoid Systems (COS), Munich Institute of Biomedical Engineering, Garching, Germany.
⁴ Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Computational Neural DNA Dynamics Lab, Department of Cognitive Science, University of California, San Diego, San Diego, CA, USA; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, San Diego, CA, USA.
⁵ Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
⁶ Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43205, USA.
⁷ Epigenetics & Neurobiology Unit, EMBL Rome, European Molecular Biology Laboratory, Via Ramarini 32, 00015 Monterotondo, Italy.
⁸ Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: gage@salk.edu.

Abstract

Long interspersed nuclear element-1 (L1 or LINE-1) is a highly abundant mobile genetic element in both humans and mice, comprising almost 20% of each genome. L1s are silenced by several mechanisms, as their uncontrolled expression has the potential to induce genomic instability. However, L1s are paradoxically expressed at high levels in differentiating neural progenitor cells. Using in vitro and in vivo techniques to modulate L1 expression, we report that L1s play a critical role in both human and mouse brain development by regulating the rate of neural differentiation in a reverse-transcription-independent manner.

Keywords: CP: Developmental biology; CP: Neuroscience; L1; LINE-1; brain development; neural progenitor cells; repetitive elements.

MeSH terms

Animals
Cell Differentiation
Genomic Instability*
Humans
Long Interspersed Nucleotide Elements
Mice
Neural Stem Cells*

Abstract

MeSH terms

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