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LINE-1 Retrotransposon expression in cancerous, epithelial and neuronal cells revealed by 5’ single-cell RNA-Seq

Wilson McKerrow, Nicole Doudican, Nicholas Frazzette, Shane A. Evans, Azucena Rocha, Larisa Kagermazova, John M. Sedivy, Nicola Neretti, John Carucci, View ORCID ProfileJef D. Boeke, View ORCID ProfileDavid Fenyö
doi: https://doi.org/10.1101/2021.01.19.427347
Wilson McKerrow
1Institute for Systems Genetics, NYU Langone Health, New York, NY, USA
2Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, USA
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Nicole Doudican
3Ronald O. Perelman Department of Dermatology, NYU Langone Health, New York, NY, USA
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Nicholas Frazzette
3Ronald O. Perelman Department of Dermatology, NYU Langone Health, New York, NY, USA
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Shane A. Evans
4Center for Computational Molecular Biology, Brown University, Providence, RI, USA
5Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA
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Azucena Rocha
4Center for Computational Molecular Biology, Brown University, Providence, RI, USA
5Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA
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Larisa Kagermazova
1Institute for Systems Genetics, NYU Langone Health, New York, NY, USA
2Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, USA
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John M. Sedivy
5Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA
6Center on the Biology of Aging, Brown University, Providence, RI, USA
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Nicola Neretti
4Center for Computational Molecular Biology, Brown University, Providence, RI, USA
5Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA
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John Carucci
3Ronald O. Perelman Department of Dermatology, NYU Langone Health, New York, NY, USA
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Jef D. Boeke
1Institute for Systems Genetics, NYU Langone Health, New York, NY, USA
2Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, USA
7Department of Biomedical Engineering, NYU Tandon School of Engineering, Brooklyn NY 11201
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  • ORCID record for Jef D. Boeke
David Fenyö
1Institute for Systems Genetics, NYU Langone Health, New York, NY, USA
2Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, USA
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  • ORCID record for David Fenyö
  • For correspondence: David@Fenyolab.org
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Abstract

LINE-1 retrotransposons are sequences capable of copying themselves to new genomic loci via an RNA intermediate. New studies implicate LINE-1 in a range of diseases, especially in the context of aging, but without an accurate understanding of where and when LINE-1 is expressed, a full accounting of its role in health and disease is not possible. We therefore developed a method – 5’ scL1seq – that makes use of a widely available library preparation method (10x Genomics 5’ single cell RNA-seq) to measure LINE-1 expression in tens of thousands of single cells. We recapitulated the known pattern of LINE-1 expression in tumors – present in cancer cells, absent from immune cells – and identified hitherto undescribed LINE-1 expression in human epithelial cells and mouse hippocampal neurons. In both cases, we saw a modest increase with age, supporting recent research connecting LINE-1 to age related diseases.

Competing Interest Statement

David Fenyö is a Founder and President of The Informatics Factory, and serves or served on the Scientific Advisory Board or consults for: Spectragen Informatics, Protein Metrics, Preverna. Jef Boeke is a Founder and Director of CDI Labs, Inc., a Founder of and consultant to Neochromosome, Inc, a Founder, SAB member of and consultant to ReOpen Diagnostics, LLC and serves or served on the Scientific Advisory Board of the following: Sangamo, Inc., Modern Meadow, Inc., Rome Therapeutics, Inc., Sample6, Inc., Tessera Therapeutics, Inc. and the Wyss Institute. John Sedivy is a cofounder of Transposon Therapeutics, Inc., serves as Chair of its Scientific Advisory Board, and consults for Astellas Innovation Management LLC, Atropos Therapeutics, Inc. and Gilead Sciences, Inc. John Carucci receives research funding from Regeneron, is a clinical investigator for Regeneron and Incyte, and prepared educational materials for Genentech.

Footnotes

  • Read filtering was added for my precise LINE-1 expression detection. Additional data from older and younger non-melanoma skin cancer patients was included. Links were added to allow others to easily recreate our method.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 04, 2022.
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LINE-1 Retrotransposon expression in cancerous, epithelial and neuronal cells revealed by 5’ single-cell RNA-Seq
Wilson McKerrow, Nicole Doudican, Nicholas Frazzette, Shane A. Evans, Azucena Rocha, Larisa Kagermazova, John M. Sedivy, Nicola Neretti, John Carucci, Jef D. Boeke, David Fenyö
bioRxiv 2021.01.19.427347; doi: https://doi.org/10.1101/2021.01.19.427347
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LINE-1 Retrotransposon expression in cancerous, epithelial and neuronal cells revealed by 5’ single-cell RNA-Seq
Wilson McKerrow, Nicole Doudican, Nicholas Frazzette, Shane A. Evans, Azucena Rocha, Larisa Kagermazova, John M. Sedivy, Nicola Neretti, John Carucci, Jef D. Boeke, David Fenyö
bioRxiv 2021.01.19.427347; doi: https://doi.org/10.1101/2021.01.19.427347

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