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SCF/c-kit signaling is required in 12-O-tetradecanoylphorbol-13-acetate-induced migration and differentiation of hair follicle melanocytes for epidermal pigmentation

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Abstract

Hair follicle melanocyte stem cells (McSCs) are responsible for hair pigmentation and also function as a major melanocyte reservoir for epidermal pigmentation. However, the molecular mechanism promoting McSCs for epidermal pigmentation remains elusive. 12-O-tetradecanoylphorbol-13-acetate (TPA) mimics key signaling involved in melanocyte growth, migration and differentiation. We therefore investigated the molecular basis for the contribution of hair follicle McSCs to epidermal pigmentation using the TPA induction model. We found that repetitive TPA treatment of female C57BL/6 mouse dorsal skin induced epidermal pigmentation by increasing the number of epidermal melanocytes. Particularly, TPA treatment induced McSCs to initiate proliferation, exit the stem cell niche and differentiate. We also demonstrated that TPA promotes melanoblast migration and differentiation in vitro. At the molecular level, TPA treatment induced robust expression of stem cell factor (SCF) in keratinocytes and c-kit in melanoblasts and melanocytes. Administration of ACK2, a neutralizing antibody against the Kit receptor, suppressed mouse epidermal pigmentation, decreased the number of epidermal melanocytes, and inhibited melanoblast migration. Taken together, our data demonstrate that TPA promotes the expansion, migration and differentiation of hair follicle McSCs for mouse epidermal pigmentation. SCF/c-kit signaling was required for TPA-induced migration and differentiation of hair follicle melanocytes. Our findings may provide an excellent model to investigate the signaling mechanisms regulating epidermal pigmentation from mouse hair follicle McSCs, and a potential therapeutic option for skin pigmentation disorders.

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Acknowledgements

This work was supported by grants from the National Nature Science Foundation of China (Grant number: 31170924, 30972645). We thank Dr. Randall B. Widelitz (University of Southern California) for carefully revising the manuscript.

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Authors and Affiliations

  1. Department of Dermatology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China

    Weiming Qiu, Hongtao Yan, Hui Tang, Guihong Yang & Jinjin Wu

  2. Chongqing Engineering Research Center of Stem Cell Therapy, Children’s Hospital, Chongqing Medical University, Chongqing, China

    Ke Yang

  3. Department of Cell Biology, The Third Military Medical University, Chongqing, 400038, China

    Xiufeng Bai & Xiaohua Lian

  4. “111” Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing, 400044, China

    Mingxing Lei

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  1. Weiming Qiu
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Qiu, W., Yang, K., Lei, M. et al. SCF/c-kit signaling is required in 12-O-tetradecanoylphorbol-13-acetate-induced migration and differentiation of hair follicle melanocytes for epidermal pigmentation. Cell Tissue Res 360, 333–346 (2015). https://doi.org/10.1007/s00441-014-2101-8

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