Cell Reports (Feb 2024)
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
Affiliations
- Tomohisa Toda
- 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; Corresponding author
- Tracy A. Bedrosian
- 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
- Simon T. Schafer
- 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
- Michael S. Cuoco
- 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
- Sara B. Linker
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
- Saeed Ghassemzadeh
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
- Lisa Mitchell
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
- Jack T. Whiteley
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
- Nicole Novaresi
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
- Aidan H. McDonald
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
- Iryna S. Gallina
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
- Hyojung Yoon
- Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Mark E. Hester
- Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Monique Pena
- 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
- Christina Lim
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
- Emelia Suljic
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
- Abed AlFatah Mansour
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
- Matthieu Boulard
- Epigenetics & Neurobiology Unit, EMBL Rome, European Molecular Biology Laboratory, Via Ramarini 32, 00015 Monterotondo, Italy
- Sarah L. Parylak
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
- Fred H. Gage
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Corresponding author
- Journal volume & issue
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Vol. 43,
no. 2
p. 113774
Abstract
Summary: 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.
