Senescent cells perturb intestinal stem cell differentiation through Ptk7 induced noncanonical Wnt and YAP signaling.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 01 2023
11 01 2023
Historique:
received:
12
11
2021
accepted:
06
12
2022
entrez:
11
1
2023
pubmed:
12
1
2023
medline:
14
1
2023
Statut:
epublish
Résumé
Cellular senescence and the senescence-associated secretory phenotype (SASP) are implicated in aging and age-related disease, and SASP-related inflammation is thought to contribute to tissue dysfunction in aging and diseased animals. However, whether and how SASP factors influence the regenerative capacity of tissues remains unclear. Here, using intestinal organoids as a model of tissue regeneration, we show that SASP factors released by senescent fibroblasts deregulate stem cell activity and differentiation and ultimately impair crypt formation. We identify the secreted N-terminal domain of Ptk7 as a key component of the SASP that activates non-canonical Wnt / Ca
Identifiants
pubmed: 36631445
doi: 10.1038/s41467-022-35487-9
pii: 10.1038/s41467-022-35487-9
pmc: PMC9834240
doi:
Substances chimiques
Ptk7 protein, mouse
EC 2.7.10.1
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
YAP-Signaling Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
156Subventions
Organisme : NIH HHS
ID : S10 OD028654
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG060906
Pays : United States
Organisme : NIH HHS
ID : S10 OD016281
Pays : United States
Informations de copyright
© 2023. The Author(s).
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