Regenerative Hair Pigmentation via Skin Organoids: Adaptive Patterning Mediated by Collagen VI and Semaphorin 3C

    July 2025 in “ Advanced Science ”
    Tingting Li, Xinzhu Li, Xiao Xiang, Jundong Huang, Xinyu Shen, Mengyue Wang, Jingwei Jiang, Sichen Shao, Zeming Li, Tian Xie, Deming Liu, Yiping Zhao, Rui Ma, Wenyu Wu, Wei Shi, Cheng‐Ming Chuong, Ji Li, Mingxing Lei
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    TLDR Collagen VI and Semaphorin 3C are important for hair pigmentation and could help treat pigmentation disorders.
    This study investigates hair pigmentation mechanisms using mouse skin organoids, focusing on melanocyte behavior. It identifies COL6A3 (Collagen type VI alpha 3 chain) and SEMA3C (Semaphorin 3C) as key factors in melanocyte function. COL6A3, secreted by fibroblasts, supports melanocyte maintenance and proliferation, while SEMA3C enhances adaptive patterning during hair regeneration. The COL6A3-CD44 signaling pathway is crucial for melanocyte survival, with CD44 inhibition reducing pigmentation effects. Additionally, the SEMA3C-NRP1 axis promotes melanocyte recruitment, enhancing hair pigmentation. These findings suggest potential therapeutic strategies for pigmentation disorders, though limitations in replicating human conditions indicate a need for advanced humanized organoid systems in future research.
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