Melanocyte stem cells in skin diseases and their potential in cell-based therapy.

Melanocytes have a complex function and play an important role in a variety of regulatory mechanisms in the human system. Melanocyte stem cells (MelSCs) serve as a reservoir to replenish the melanocytes by regenerating new ones, and they are capable of self-renewal and differentiation to maintain their homeostasis, repair, and regeneration in tissues. The numerical decrease and functional impairment of MelSCs may be closely related to the development and treatment response of many skin diseases. However, the current knowledge about MelSCs mainly comes from studies in mice, and little is known about human MelSC markers; especially, their markers are still unclear or lack consensus. This leads to uncertainty in clinical findings, which further limits our comprehensive understanding of pigmentary disorders and also hinders the progress of new treatments. Thus, in this review article, combined with our previous and current work, we summarize and update the recent advances in MelSC research, including the molecular markers of human MelSCs and their niche, as well as the association of MelSCs with skin diseases, including vitiligo, hair greying, and melanoma. Due to the limited tools available to explore the identified characteristics of human MelSCs, pluripotent stem cells can provide a new research model for further study, especially combined with CRISPR/Cas9 technology. The visualization of human MelSCs' development and differentiation can help to identify their molecular characteristics and understand their cellular fate dynamically, which will allow us not only to further explore their roles in associated diseases, but also to achieve MelSC-based cellular therapy.