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Senescent cells deposit intracellular contents through adhesion-dependent fragmentation

Matej Durik, Daniel Sampaio Gonçalves, Coralie Spiegelhalter, Nadia Messaddeq, View ORCID ProfileWilliam M. Keyes
doi: https://doi.org/10.1101/2023.01.11.523642
Matej Durik
1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France
2UMR7104, Centre National de la Recherche Scientifique (CNRS), Illkirch, France
3U1258, Institut National de la Santé et de la Recherche Médicale (INSERM), Illkirch, France
4Université de Strasbourg, Illkirch, France
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  • For correspondence: bill.keyes@igbmc.fr durikm@igbmc.fr
Daniel Sampaio Gonçalves
1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France
2UMR7104, Centre National de la Recherche Scientifique (CNRS), Illkirch, France
3U1258, Institut National de la Santé et de la Recherche Médicale (INSERM), Illkirch, France
4Université de Strasbourg, Illkirch, France
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Coralie Spiegelhalter
1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France
2UMR7104, Centre National de la Recherche Scientifique (CNRS), Illkirch, France
3U1258, Institut National de la Santé et de la Recherche Médicale (INSERM), Illkirch, France
4Université de Strasbourg, Illkirch, France
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Nadia Messaddeq
1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France
2UMR7104, Centre National de la Recherche Scientifique (CNRS), Illkirch, France
3U1258, Institut National de la Santé et de la Recherche Médicale (INSERM), Illkirch, France
4Université de Strasbourg, Illkirch, France
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William M. Keyes
1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France
2UMR7104, Centre National de la Recherche Scientifique (CNRS), Illkirch, France
3U1258, Institut National de la Santé et de la Recherche Médicale (INSERM), Illkirch, France
4Université de Strasbourg, Illkirch, France
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  • ORCID record for William M. Keyes
  • For correspondence: bill.keyes@igbmc.fr durikm@igbmc.fr
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ABSTRACT

Cellular senescence is a complex cell state with roles in tumor suppression, embryonic development and wound repair. However, when misregulated, senescence contributes to aging and disease. Here we identify that senescent cells generate/break off large membranebound fragments of themselves through cell-to-cell adhesion. We designate these as senescent-cell adhesion fragments (SCAFs) which were present in all types of senescent cell examined. We show they contain many organelles from the original cell, but without nuclear material. Quantitative and dynamic profiling shows that SCAFs are large, may persist for a number of days, but rupture and release their contents onto neighboring cells. Protein profiling identifies that SCAFs contain a complex proteome including immune recruitment factors and damage-associated molecular patterns (DAMPs). Functional studies reveal that SCAFs activate signatures related to wound healing and cancer, and promote invasion and migration. Altogether, we uncover an additional cellular feature of senescent cells, by which they deposit intracellular contents on other cells. We speculate this may aid in boosting immune responses, but in chronic situations, may contribute to debris buildup, inflammaging and age-associated changes.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 12, 2023.
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Senescent cells deposit intracellular contents through adhesion-dependent fragmentation
Matej Durik, Daniel Sampaio Gonçalves, Coralie Spiegelhalter, Nadia Messaddeq, William M. Keyes
bioRxiv 2023.01.11.523642; doi: https://doi.org/10.1101/2023.01.11.523642
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Senescent cells deposit intracellular contents through adhesion-dependent fragmentation
Matej Durik, Daniel Sampaio Gonçalves, Coralie Spiegelhalter, Nadia Messaddeq, William M. Keyes
bioRxiv 2023.01.11.523642; doi: https://doi.org/10.1101/2023.01.11.523642

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