{"id":497566,"date":"2024-01-26T19:00:00","date_gmt":"2024-01-27T00:00:00","guid":{"rendered":"https:\/\/platohealth.ai\/sexual-dimorphism-in-melanocyte-stem-cell-behavior-reveals-combinational-therapeutic-strategies-for-cutaneous-repigmentation-nature-communications\/"},"modified":"2024-01-27T07:47:27","modified_gmt":"2024-01-27T12:47:27","slug":"sexual-dimorphism-in-melanocyte-stem-cell-behavior-reveals-combinational-therapeutic-strategies-for-cutaneous-repigmentation-nature-communications","status":"publish","type":"post","link":"https:\/\/platohealth.ai\/sexual-dimorphism-in-melanocyte-stem-cell-behavior-reveals-combinational-therapeutic-strategies-for-cutaneous-repigmentation-nature-communications\/","title":{"rendered":"Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for cutaneous repigmentation – Nature Communications","gt_translate_keys":[{"key":"rendered","format":"text"}]},"content":{"rendered":"
Several excellent mouse models of vitiligo have been established to study T cell autoimmunity against epidermal melanocytes21<\/a>,22<\/a>,23<\/a><\/sup>. In addition to eliminating CD8\u2009+\u2009T cell activity, replenishing the epidermal melanocyte population to regain pigmentation is another important aspect of vitiligo therapy. However, existing models of vitiligo are not ideal for studying the mechanisms of hair follicle McSC activation and migration for epidermal translocation. In one model, overexpression of Kitl (Stem cell factor) results in artificially high levels of melanocyte localization to the epidermis, thus potentially obscuring data to be collected for the natural UVB-induced process of translocation, as it would occur in human patients21<\/a>,22<\/a><\/sup>. In another, auto-immunity results in induced follicle McSC loss and hair graying23<\/a><\/sup>, such that the reservoir of McSCs is significantly depleted or no longer exists, thus eliminating the source of translocating melanocytes. In this study, we primarily focus on determining methods to promote epidermal melanocyte repopulation. Thus, we chose adult homeostasis of C57Bl\/6 wildtype mice as a model to understand the mechanisms of UVB-induced stimulation of McSC activation and migration.<\/p>\n McSCs of the murine dorsal skin are located exclusively within the hair follicle stem cell niche (the bulge) and are not present in the IFE, similar to the distribution of skin melanocytes affected in human vitiligo patients. To visualize cutaneous McSCs, we utilized Dct-rtTA; Tre-H2B-GFP<\/i> (DG<\/i>) mice18<\/a>,24<\/a><\/sup>, in which McSC and differentiated melanocyte nuclei are labeled by H2B-GFP (Histone2B-Green Fluorescent Protein) following doxycycline administration25<\/a><\/sup> (Fig. 1A<\/a>). To induce McSC migration to the IFE, we shaved the hair from the dorsal skin and irradiated with UVB (280\u2013315\u2009nm, dosage 2.2\u2009J\/m2<\/sup>) three times at 8 weeks of age (Fig. 1A<\/a>). This procedure results in a robust number of migrated melanocytes (Fig. 1B<\/a>), but does not induce McSC DNA damage, or significant apoptosis 24\u2009h (24\u2009h) post irradiation (Supplemental Fig. 1A, B<\/a>). These data are consistent with previous studies showing that short wavelength UVB exhibits low penetration through the epidermal layer26<\/a><\/sup>, and indicate that McSC migration is likely not regulated by McSC DNA damage or related to wound healing14<\/a>,27<\/a><\/sup>.<\/p>\n