A Wnt5a-Cdc42 Axis Controls Aging and Rejuvenation of Hair-Follicle Stem Cells

    October 2020 in “ bioRxiv (Cold Spring Harbor Laboratory) ”
    Rajiv Lochan Tiwari, Pratibha Mishra, Nicola Martin, Nikhil Oommen George, Vadim Sakk, Karin Soller, Kodandaramireddy Nalapareddy, Kalpana Nattamai, Karin Scharffetter‐­Kochanek, Maria Carolina Florian, Hartmut Geiger
    TLDR Aging hair follicle stem cells can be rejuvenated by inhibiting Cdc42.
    The study demonstrated that aging in hair follicle stem cells (HFSCs) was associated with a decrease in canonical Wnt signaling and an increase in non-canonical Wnt5a signaling, which antagonized the former. This shift led to elevated activity and altered distribution of the small RhoGTPase Cdc42 within HFSCs. By using CASIN, a pharmacological inhibitor of Cdc42, researchers were able to restore canonical Wnt signaling in aged HFSCs. In vivo treatment of aged mice with CASIN successfully induced the onset of anagen and increased the percentage of anagen skin areas, suggesting that the aging-associated functional deficits in HFSCs were intrinsic and could be mitigated through targeted pharmacological interventions.
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