de Duve Institute, Université catholique de Louvain, 1200, Brussels, Belgium.
Nat Commun. 2022 Aug 1;13(1):4449. doi: 10.1038/s41467-022-32239-7.
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.
毛囊经历由毛囊干细胞（HFSCs）驱动的再生周期。虽然 β-连环蛋白依赖性经典 Wnt 信号已被广泛研究，并与 HFSC 激活和命运决定有关，但关于 Wnt 信号中非 β-连环蛋白依赖性在 HFSCs 中的功能知之甚少。在这项研究中，我们研究了 Wnt 受体 ROR2 在 HFSCs 中的功能作用。通过分析 Ror2 耗尽的 HFSCs，我们揭示了 ROR2 不仅对调节 Wnt 激活信号至关重要，该信号负责 HFSC 的激活和自我更新，而且还需要维持适当的 ATM/ATR 依赖性 DNA 损伤反应，这对于 HFSCs 的长期维持是必不可少的。在分析缺乏 β-连环蛋白的 HFSCs 时，我们确定了 ROR2-PKC 信号在保护 β-连环蛋白缺失的 HFSCs 免受干细胞池损失方面的代偿作用。总之，我们的研究揭示了 ROR2 在调节干细胞自我更新和维持中的以前未被认识的作用。
