Arl13b controls basal cell stemness properties and Hedgehog signaling in the mouse epididymis.
Basal cell
Epididymis
Hedgehog signaling
Primary cilia
Resident stem cells
Tissue regeneration
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
19 Oct 2022
19 Oct 2022
Historique:
received:
28
06
2022
accepted:
22
09
2022
revised:
09
09
2022
entrez:
19
10
2022
pubmed:
20
10
2022
medline:
22
10
2022
Statut:
epublish
Résumé
Epithelial cells orchestrate a series of intercellular signaling events in response to tissue damage. While the epididymis is composed of a pseudostratified epithelium that controls the acquisition of male fertility, the maintenance of its integrity in the context of tissue damage or inflammation remains largely unknown. Basal cells of the epididymis contain a primary cilium, an organelle that controls cellular differentiation in response to Hedgehog signaling cues. Hypothesizing its contribution to epithelial homeostasis, we knocked out the ciliary component ARL13B in keratin 5-positive basal cells. In this model, the reduced size of basal cell primary cilia was associated with impaired Hedgehog signaling and the loss of KRT5, KRT14, and P63 basal cell markers. When subjected to tissue injury, the epididymal epithelium from knock-out mice displayed imbalanced rates of cell proliferation/apoptosis and failed to properly regenerate in vivo. This response was associated with changes in the transcriptomic landscape related to immune response, cell differentiation, cell adhesion, and triggered severe hypoplasia of the epithelium. Together our results indicate that the ciliary GTPase, ARL13B, participates in the transduction of the Hedgehog signaling pathway to maintain basal cell stemness needed for tissue regeneration. These findings provide new insights into the role of basal cell primary cilia as safeguards of pseudostratified epithelia.
Identifiants
pubmed: 36261680
doi: 10.1007/s00018-022-04570-1
pii: 10.1007/s00018-022-04570-1
doi:
Substances chimiques
ADP-Ribosylation Factors
EC 3.6.5.2
Arl13b protein, mouse
0
GTP Phosphohydrolases
EC 3.6.1.-
Hedgehog Proteins
0
Keratin-5
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
556Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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