The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration

Ritschka, B., Storer, M., Mas, A., Heinzmann, F., Ortells, M. C., Morton, J. P. , Sansom, O. J. , Zender, L. and Keyes, W. M. (2017) The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes and Development, 31(2), pp. 172-183. (doi: 10.1101/gad.290635.116) (PMID:28143833)

Abstract

Senescence is a form of cell cycle arrest induced by stress such as DNA damage and oncogenes. However, while arrested, senescent cells secrete a variety of proteins collectively known as the senescence-associated secretory phenotype (SASP), which can reinforce the arrest and induce senescence in a paracrine manner. However, the SASP has also been shown to favor embryonic development, wound healing, and even tumor growth, suggesting more complex physiological roles than currently understood. Here we uncover timely new functions of the SASP in promoting a proregenerative response through the induction of cell plasticity and stemness. We show that primary mouse keratinocytes transiently exposed to the SASP exhibit increased expression of stem cell markers and regenerative capacity in vivo. However, prolonged exposure to the SASP causes a subsequent cell-intrinsic senescence arrest to counter the continued regenerative stimuli. Finally, by inducing senescence in single cells in vivo in the liver, we demonstrate that this activates tissue-specific expression of stem cell markers. Together, this work uncovers a primary and beneficial role for the SASP in promoting cell plasticity and tissue regeneration and introduces the concept that transient therapeutic delivery of senescent cells could be harnessed to drive tissue regeneration.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Morton, Professor Jen and Sansom, Professor Owen
• Authors: Ritschka, B., Storer, M., Mas, A., Heinzmann, F., Ortells, M. C., Morton, J. P., Sansom, O. J., Zender, L., and Keyes, W. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Genes and Development
• Publisher: Cold Spring Harbor Laboratory Press
• ISSN: 0890-9369
• ISSN (Online): 1549-5477
• Published Online: 31 January 2017
• Copyright Holders: Copyright © 2017 Ritschka et al.
• First Published: First published in Genes and Development 31(2):172-183
• Publisher Policy: Reproduced under a Creative Commons License