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The intensities of canonical senescence biomarkers integrate the duration of cell-cycle withdrawal

View ORCID ProfileHumza M. Ashraf, Brianna Fernandez, Sabrina L. Spencer
doi: https://doi.org/10.1101/2023.03.18.533242
Humza M. Ashraf
1Department of Biochemistry, University of Colorado, Boulder, CO 80303
2BioFrontiers Institute, University of Colorado, Boulder, CO 80303
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  • ORCID record for Humza M. Ashraf
Brianna Fernandez
1Department of Biochemistry, University of Colorado, Boulder, CO 80303
2BioFrontiers Institute, University of Colorado, Boulder, CO 80303
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Sabrina L. Spencer
1Department of Biochemistry, University of Colorado, Boulder, CO 80303
2BioFrontiers Institute, University of Colorado, Boulder, CO 80303
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  • For correspondence: sabrina.spencer@colorado.edu
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Abstract

Senescence, a state of permanent cell-cycle withdrawal, is difficult to distinguish from quiescence, a transient state of cell-cycle withdrawal. This difficulty arises because quiescent and senescent cells are defined by overlapping biomarkers, raising the question of whether quiescence and senescence are truly distinct states. To address this, we used single-cell time-lapse imaging to distinguish slow-cycling quiescent cells from bona fide senescent cells after chemotherapy treatment, followed immediately by staining for various senescence biomarkers. We found that the staining intensity of multiple senescence biomarkers is graded rather than binary and primarily reflects the duration of cell-cycle withdrawal, rather than senescence per se. Together, our data suggest that quiescence and senescence are not distinct cellular states but rather fall on a continuum of cell-cycle withdrawal, where the intensities of canonical senescence biomarkers reflect the likelihood of cell-cycle re-entry.

Competing Interest Statement

The authors have declared no competing interest.

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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 March 21, 2023.
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The intensities of canonical senescence biomarkers integrate the duration of cell-cycle withdrawal
Humza M. Ashraf, Brianna Fernandez, Sabrina L. Spencer
bioRxiv 2023.03.18.533242; doi: https://doi.org/10.1101/2023.03.18.533242
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The intensities of canonical senescence biomarkers integrate the duration of cell-cycle withdrawal
Humza M. Ashraf, Brianna Fernandez, Sabrina L. Spencer
bioRxiv 2023.03.18.533242; doi: https://doi.org/10.1101/2023.03.18.533242

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