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- Title
ROR2 regulates self-renewal and maintenance of hair follicle stem cells.
- Authors
Veltri, Anthony; Lang, Christopher M. R.; Cangiotti, Gaia; Chan, Chim Kei; Lien, Wen-Hui
- Abstract
Hair follicles undergo cycles of regeneration fueled by hair follicle stem cells (HFSCs). While β-catenin-dependent canonical Wnt signaling has been extensively studied and implicated in HFSC activation and fate determination, very little is known about the function of β-catenin-independent Wnt signaling in HFSCs. In this study, we investigate the functional role of ROR2, a Wnt receptor, in HFSCs. By analyzing Ror2-depleted HFSCs, we uncover that ROR2 is not only essential to regulate Wnt-activated signaling that is responsible for HFSC activation and self-renewal, but it is also required to maintain proper ATM/ATR-dependent DNA damage response, which is indispensable for the long-term maintenance of HFSCs. In analyzing HFSCs lacking β-catenin, we identify a compensatory role of ROR2-PKC signaling in protecting β-catenin-null HFSCs from the loss of stem cell pool. Collectively, our study unveils a previously unrecognized role of ROR2 in regulation of stem cell self-renewal and maintenance. Wnt signaling functions in tissue homeostasis and tumorigenesis. Here the authors show that ROR2, a Wnt receptor, plays roles not only in transducing Wnt signaling, but also in regulation of DNA damage response critical for stem cell maintenance.
- Subjects
HAIR follicles; STEM cells; WNT signal transduction; CELLULAR control mechanisms; DNA damage; FUEL cycle
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-32239-7