Transposable Element Derepression-mediated IFN-I Signaling Enhances Stem/Progenitor Cell Activity After Irradiation Article Swipe
Davide Cinat
,
Ryan van der Wal
,
Mirjam Baanstra
,
Abel Soto-Gamez
,
Anne L. Jellema-de Bruin
,
Uilke Brouwer
,
Marc‐Jan van Goethem
,
Marcel A.T.M. van Vugt
,
Lara Barazzuol
,
Robert P. Coppes
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.02.14.580306
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.02.14.580306
Radiotherapy is a mainstay in cancer treatment, aiming to maximize DNA damage in tumors while minimizing harm to surrounding healthy tissues. However, the collateral damage to normal tissues, especially stem/progenitor cells essential for tissue regeneration and organ function, remains a significant challenge. Here, we investigate the molecular responses to photon and proton irradiation, two key modalities in head and neck cancer treatment, using organoids. Multiomics analysis reveals a stronger double-stranded RNA (dsRNA)-induced type I interferon (IFN-I) response following proton irradiation, driven by loss of heterochromatin regulators and derepression of transposable elements (TEs). This response, mediated by the cytoplasmic sensor RIG-I, enhances the inflammatory signaling initiated by the canonical dsDNA sensors cGAS and ZBP1. Genetic and pharmacological modulation of IFN-I signaling in vitro and in vivo demonstrates its critical role in enhancing stem/progenitor cell activity post-irradiation. Our findings reveal a pro-regenerative role of TE derepression-mediated IFN-I response suggesting this pathway as a promising therapeutic target to mitigate radiation-induced side effects. Teaser Transposable element-mediated type I interferon signaling enhances stem/progenitor cell activity after irradiation.
Related Topics
Concepts
Derepression
Progenitor cell
Transposable element
Stem cell
Interferon
Progenitor
Cell biology
Chemistry
Biology
Genetics
Gene
Genome
Gene expression
Psychological repression
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.02.14.580306
- https://www.biorxiv.org/content/biorxiv/early/2024/02/15/2024.02.14.580306.full.pdf
- OA Status
- green
- Cited By
- 5
- References
- 72
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4391846267
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4391846267Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2024.02.14.580306Digital Object Identifier
- Title
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Transposable Element Derepression-mediated IFN-I Signaling Enhances Stem/Progenitor Cell Activity After IrradiationWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-02-15Full publication date if available
- Authors
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Davide Cinat, Ryan van der Wal, Mirjam Baanstra, Abel Soto-Gamez, Anne L. Jellema-de Bruin, Uilke Brouwer, Marc‐Jan van Goethem, Marcel A.T.M. van Vugt, Lara Barazzuol, Robert P. CoppesList of authors in order
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https://doi.org/10.1101/2024.02.14.580306Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2024/02/15/2024.02.14.580306.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2024/02/15/2024.02.14.580306.full.pdfDirect OA link when available
- Concepts
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Derepression, Progenitor cell, Transposable element, Stem cell, Interferon, Progenitor, Cell biology, Chemistry, Biology, Genetics, Gene, Genome, Gene expression, Psychological repressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
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5Total citation count in OpenAlex
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2024: 5Per-year citation counts (last 5 years)
- References (count)
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72Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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