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...
| Autores: | , , , , , , , , |
|---|---|
| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2017 |
| País: | España |
| Recursos: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/68900 |
| Acesso em linha: | http://hdl.handle.net/10230/68900 http://dx.doi.org/10.1101/gad.290635.116 |
| Access Level: | acceso abierto |
| Palavra-chave: | Senescence Plasticity Stem cells Papilloma CD34 SASP |
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The senescence-associated secretory phenotype induces cellular plasticity and tissue regenerationRitschka, Birgit, 1985-Storer, Mekayla, 1981-Mas Malavila, AlbaHeinzmann, FlorianOrtells Campos, Mª Carmen, 1984-Morton, Jennifer P.Sansom, Owen J.Zender, LarsKeyes, William M., 1973-SenescencePlasticityStem cellsPapillomaCD34SASPSenescence 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.We thank Ryan Driskell and Fiona Watt for technical advice, Guillaume Filion and Panagiotis Papasaikas for advice on statistics, Pura Muñoz-Cánoves for β-actin GFP mice, the Centre for Genomic Regulation Bioinformatics unit for assistance, and Pura Muñoz-Cánoves and Juan Valcarcel for critical reading of the manuscript. M.S. and B.R. were supported with fellowships from the “La Caixa” foundation. This work was funded by grants SAF2010-18829 and SAF2013-49082-P (to W.M.K.) from the Spanish Ministry for Economy and Competitiveness, the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) from the Generalitat de Catalunya, and Centre for Genomic Regulation core funding.Cold Spring Harbor Laboratory Press (CSHL Press)202420242017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/68900http://dx.doi.org/10.1101/gad.290635.116reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésGenes & Development. 2017 Jan 15;31(2):172-83info:eu-repo/grantAgreement/ES/3PN/SAF2010-18829info:eu-repo/grantAgreement/ES/1PE/SAF2013-49082-P© 2017 Ritschka et al.; Published by Cold Spring Harbor Laboratory Press. This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.http://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/689002026-06-12T07:21:37Z |
| dc.title.none.fl_str_mv |
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration |
| title |
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration |
| spellingShingle |
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration Ritschka, Birgit, 1985- Senescence Plasticity Stem cells Papilloma CD34 SASP |
| title_short |
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration |
| title_full |
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration |
| title_fullStr |
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration |
| title_full_unstemmed |
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration |
| title_sort |
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration |
| dc.creator.none.fl_str_mv |
Ritschka, Birgit, 1985- Storer, Mekayla, 1981- Mas Malavila, Alba Heinzmann, Florian Ortells Campos, Mª Carmen, 1984- Morton, Jennifer P. Sansom, Owen J. Zender, Lars Keyes, William M., 1973- |
| author |
Ritschka, Birgit, 1985- |
| author_facet |
Ritschka, Birgit, 1985- Storer, Mekayla, 1981- Mas Malavila, Alba Heinzmann, Florian Ortells Campos, Mª Carmen, 1984- Morton, Jennifer P. Sansom, Owen J. Zender, Lars Keyes, William M., 1973- |
| author_role |
author |
| author2 |
Storer, Mekayla, 1981- Mas Malavila, Alba Heinzmann, Florian Ortells Campos, Mª Carmen, 1984- Morton, Jennifer P. Sansom, Owen J. Zender, Lars Keyes, William M., 1973- |
| author2_role |
author author author author author author author author |
| dc.subject.none.fl_str_mv |
Senescence Plasticity Stem cells Papilloma CD34 SASP |
| topic |
Senescence Plasticity Stem cells Papilloma CD34 SASP |
| description |
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. |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2017 2024 2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/68900 http://dx.doi.org/10.1101/gad.290635.116 |
| url |
http://hdl.handle.net/10230/68900 http://dx.doi.org/10.1101/gad.290635.116 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Genes & Development. 2017 Jan 15;31(2):172-83 info:eu-repo/grantAgreement/ES/3PN/SAF2010-18829 info:eu-repo/grantAgreement/ES/1PE/SAF2013-49082-P |
| dc.rights.none.fl_str_mv |
http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by-nc/4.0/ |
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openAccess |
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application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Cold Spring Harbor Laboratory Press (CSHL Press) |
| publisher.none.fl_str_mv |
Cold Spring Harbor Laboratory Press (CSHL Press) |
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reponame:Repositorio Digital de la UPF instname:Universitat Pompeu Fabra |
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Universitat Pompeu Fabra |
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Repositorio Digital de la UPF |
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Repositorio Digital de la UPF |
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