Arl13b controls basal cell stemness properties and Hedgehog signaling in the mouse epididymis.

Autor: Girardet L; Faculty of Medicine, Department of Obstetrics, Gynecology and Reproduction, Université Laval, CHU de Québec Research Center (CHUL), Quebec City, QC, Canada., Cyr DG; Faculty of Medicine, Department of Obstetrics, Gynecology and Reproduction, Université Laval, CHU de Québec Research Center (CHUL), Quebec City, QC, Canada.; Laboratory for Reproductive Toxicology, INRS-Centre Armand-Frappier Santé Biotechnologie, Université du Québec, Laval, QC, Canada., Belleannée C; Faculty of Medicine, Department of Obstetrics, Gynecology and Reproduction, Université Laval, CHU de Québec Research Center (CHUL), Quebec City, QC, Canada. Clemence.Belleannee@crchudequebec.ulaval.ca.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2022 Oct 19; Vol. 79 (11), pp. 556. Date of Electronic Publication: 2022 Oct 19.
DOI: 10.1007/s00018-022-04570-1
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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