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CXCL12 regulates differentiation of human immature melanocyte precursors as well as their migration

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Abstract

Melanocyte stem cells (McSCs) are localized in the bulge region of hair follicles and supply melanocytes, which determine hair color by synthesizing melanin. Ectopic differentiation of McSCs, which are usually undifferentiated in the bulge region, causes depletion of McSCs and results in hair graying. Therefore, to prevent hair graying, it is essential to maintain McSCs in the bulge region, but the mechanism of McSC maintenance remains unclear. To address this issue, we investigated the role of CXCL12, a chemokine which was previously suggested to induce migration of melanocyte lineage cells, as a niche component of McSCs. Immunohistological analysis revealed that CXCL12 was highly expressed in the bulge region of human hair follicles. CXCL12 mRNA expression level was significantly lower in white hairs plucked from human scalps than in black hairs. CXCL12 attracted the migration of early-passage normal human epidermal melanocytes (eNHEMs), an in vitro model of McSCs, which had characteristics of immature melanocyte precursors. We also found that CXCL12 suppressed their differentiation. These results suggest that CXCL12 regulates differentiation of McSCs as well as their proper localization, and maintaining McSCs by regulating CXCL12 expression level in the bulge region may be a key to preventing hair graying.

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References

  1. Avniel S, Arik Z, Maly A, Sagie A, Basst HB, Yahana MD, Weiss ID, Pal B, Wald O, Ad-El D, Fujii N, Arenzana-Seisdedos F, Jung S, Galun E, Gur E, Peled A (2006) Involvement of the CXCL12/CXCR4 pathway in the recovery of skin following burns. J Invest Dermatol 126:468–476

    Article  CAS  PubMed  Google Scholar 

  2. Belmadani A, Jung H, Ren D, Miller RJ (2009) The chemokine SDF-1/CXCL12 regulates the migration of melanocyte progenitors in mouse hair follicles. Differentiation 77:395–411

    Article  CAS  PubMed  Google Scholar 

  3. Brizzi MF, Tarone G, Defilippi P (2012) Extracellular matrix, integrins, and growth factors as tailors of the stem cell niche. Curr Opin Cell Biol 24:645–651

    Article  CAS  PubMed  Google Scholar 

  4. Choi HR, Byun SY, Kwon SH, Park KC (2015) Niche interactions in epidermal stem cells. World J Stem Cells 7:495–501

    Article  PubMed  PubMed Central  Google Scholar 

  5. Choi YJ, Yoon TJ, Lee YH (2008) Changing expression of the genes related to human hair graying. Eur J Dermatol 18:397–399

    CAS  PubMed  Google Scholar 

  6. Gattazzo F, Urciuolo A, Bonaldo P (2014) Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim Biophys Acta 1840:2506–2519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ghosh MC, Collins GD, Vandanmagsar B, Patel K, Brill M, Carter A, Lustig A, Becker KG, Wood WW III, Emeche CD, French AD, O’Connell MP, Xu M, Weeraratna AT, Taub DD (2009) Activation of Wnt5A signaling is required for CXC chemokine ligand 12-mediated T-cell migration. Blood 114:1366–1373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hachiya A, Sriwiriyanont P, Kobayashi T, Nagasawa A, Yoshida H, Ohuchi A, Kitahara T, Visscher MO, Takema Y, Tsuboi R, Boissy RE (2009) Stem cell factor-KIT signalling plays a pivotal role in regulating pigmentation in mammalian hair. J Pathol 218:30–39

    Article  CAS  PubMed  Google Scholar 

  9. Inomata K, Aoto T, Binh NT, Okamoto N, Tanimura S, Wakayama T, Iseki S, Hara E, Masunaga T, Shimizu H, Nishimura EK (2009) Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation. Cell 137:1088–1099

    Article  CAS  PubMed  Google Scholar 

  10. Keogh EV, Walsh RJ (1965) Rate of greying of human hair. Nature 207:877–878

    Article  CAS  PubMed  Google Scholar 

  11. Lee E, Han J, Kim K, Choi H, Cho EG, Lee TR (2013) CXCR7 mediates SDF1-induced melanocyte migration. Pigment Cell Melanoma Res 26:58–66

    Article  CAS  PubMed  Google Scholar 

  12. Millar SE (2002) Molecular mechanisms regulating hair follicle development. J Invest Dermatol 118:216–225

    Article  CAS  PubMed  Google Scholar 

  13. Nishimura EK, Jordan SA, Oshima H, Yoshida H, Osawa M, Moriyama M, Jackson IJ, Barrandon Y, Miyachi Y, Nishikawa S (2002) Dominant role of the niche in melanocyte stem-cell fate determination. Nature 416:854–860

    Article  CAS  PubMed  Google Scholar 

  14. Nishimura EK, Suzuki M, Igras V, Du J, Lonning S, Miyachi Y, Roes J, Beermann F, Fisher DE (2010) Key roles for transforming growth factor beta in melanocyte stem cell maintenance. Cell Stem Cell 6:130–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pajonk F, Vlashi E (2013) Characterization of the stem cell niche and its importance in radiobiological response. Semin Radiat Oncol 23:237–241

    Article  PubMed  PubMed Central  Google Scholar 

  16. Panhard S, Lozano I, Loussouarn G (2012) Greying of the human hair: a worldwide survey, revisiting the ‘50’ rule of thumb. Br J Dermatol 167:865–873

    Article  CAS  PubMed  Google Scholar 

  17. Sato A, Yamamoto H, Sakane H, Koyama H, Kikuchi A (2010) Wnt5a regulates distinct signalling pathways by binding to Frizzled2. EMBO J 29:41–54

    Article  CAS  PubMed  Google Scholar 

  18. Sugiyama T, Kohara H, Noda M, Nagasawa T (2006) Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25:977–988

    Article  CAS  PubMed  Google Scholar 

  19. Tanimura S, Tadokoro Y, Inomata K, Binh NT, Nishie W, Yamazaki S, Nakauchi H, Tanaka Y, McMillan JR, Sawamura D, Yancey K, Shimizu H, Nishimura EK (2011) Hair follicle stem cells provide a functional niche for melanocyte stem cells. Cell Stem Cell 8:177–187

    Article  CAS  PubMed  Google Scholar 

  20. Yamada T, Hasegawa S, Inoue Y, Date Y, Arima M, Yagami A, Iwata Y, Takahashi M, Yamamoto N, Mizutani H, Nakata S, Matsunaga K, Akamatsu H (2014) Accelerated differentiation of melanocyte stem cells contributes to the formation of hyperpigmented maculae. Exp Dermatol 23:652–658

    Article  CAS  PubMed  Google Scholar 

  21. Yamada T, Hasegawa S, Inoue Y, Date Y, Yamamoto N, Mizutani H, Nakata S, Matsunaga K, Akamatsu H (2013) Wnt/β-catenin and kit signaling sequentially regulate melanocyte stem cell differentiation in UVB-induced epidermal pigmentation. J Invest Dermatol 133:2753–2762

    Article  CAS  PubMed  Google Scholar 

  22. Yamauchi A, Hadjur C, Takahashi T, Suzuki I, Hirose K, Mahe YF (2013) Human skin melanocyte migration towards stromal cell-derived factor-1α demonstrated by optical real-time cell mobility assay: modulation of their chemotactic ability by α-melanocyte-stimulating hormone. Exp Dermatol 22:664–667

    Article  CAS  PubMed  Google Scholar 

  23. Zhang H, Zhu NX, Huang K, Cai BZ, Zeng Y, Xu YM, Liu Y, Yuan YP, Lin CM (2016) iTRAQ-based quantitative proteomic comparison of early- and late-passage human dermal papilla cell secretome in relation to inducing hair follicle regeneration. PLoS One 11:e0167474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are grateful to N. Goshima (Cellisis Co., Ltd., Aichi, Japan) for her support in preparing the manuscript.

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TY and SH designed the research study. TY, MA, YI, TK, SN and NY performed the research. TY, SH, SN, KS and HA carried out the data analysis and wrote the manuscript. All authors critically revised the manuscript and approved the final manuscript.

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Correspondence to Takaaki Yamada.

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The authors state no conflict of interest.

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Yamada, T., Hasegawa, S., Hasebe, Y. et al. CXCL12 regulates differentiation of human immature melanocyte precursors as well as their migration. Arch Dermatol Res 311, 55–62 (2019). https://doi.org/10.1007/s00403-018-1880-2

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  • DOI: https://doi.org/10.1007/s00403-018-1880-2

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