ROR2 regulates self-renewal and maintenance of hair follicle stem cells

Anthony Veltri, Christopher M. R. Lang, Gaia Cangiotti, Chim Kei Chan and Wen-Hui Lien ()
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Anthony Veltri: de Duve Institute, Université catholique de Louvain
Christopher M. R. Lang: de Duve Institute, Université catholique de Louvain
Gaia Cangiotti: de Duve Institute, Université catholique de Louvain
Chim Kei Chan: de Duve Institute, Université catholique de Louvain
Wen-Hui Lien: de Duve Institute, Université catholique de Louvain

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32239-7

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