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

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 p...

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Published in:Genes & development Vol. 31; no. 2; p. 172
Main Authors: Ritschka, Birgit, Storer, Mekayla, Mas, Alba, Heinzmann, Florian, Ortells, Mari Carmen, Morton, Jennifer P, Sansom, Owen J, Zender, Lars, Keyes, William M
Format: Journal Article
Language:English
Published: United States 15.01.2017
Subjects:
Animals
Biomarkers - metabolism
Cell Plasticity - genetics
Cell Plasticity - physiology
Cells, Cultured
Cellular Senescence - genetics
Cellular Senescence - physiology
Epithelial Cells - cytology
Epithelial Cells - physiology
Female
Gene Deletion
Gene Expression Regulation, Developmental - genetics
Keratinocytes - cytology
Keratinocytes - physiology
Liver - cytology
Liver - physiology
Mice
Mice, Inbred C57BL
NF-kappa B - genetics
Phenotype
Regeneration - genetics
Regeneration - physiology
Secretory Pathway - genetics
Secretory Pathway - physiology
Stem Cells - metabolism
senescence
stem cells
plasticity
CD34
SASP
papilloma
ISSN:1549-5477, 1549-5477
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Summary: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.
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ISSN:1549-5477
1549-5477
DOI:10.1101/gad.290635.116