在过去的十年中，黑色素瘤在新的癌症治疗领域取得了领先地位，治疗期生存率取得了令人瞩目的进展，但总体生存率的改善相对较小。黑色素瘤呈现出异质性和转录可塑性，重现了不同的黑色素细胞发育状态和表型，使其能够适应并最终逃避即使是最先进的治疗。尽管我们对黑色素瘤生物学和遗传学的理解取得了显著进展，但黑色素细胞的起源仍然备受争议，因为黑色素干细胞和成熟黑色素细胞都可能被转化。动物模型和高通量单细胞测序方法为解决这个问题开辟了新的机会。在这里，我们讨论了黑色素细胞从神经嵴出发的黑素细胞旅程，到在多个组织中驻留的完全成熟的色素黑色素细胞。我们描述了对黑色素细胞生物学以及它们所居住的不同黑色素细胞亚群和微环境的新认识，以及这如何提供独特的洞察力，了解黑色素瘤的发生和发展。我们强调了对黑色素瘤的异质性和转录可塑性的最新发现，以及它们对令人兴奋的新研究领域和治疗机会的影响。黑色素细胞生物学的教训揭示了一种机制，即本来存在于保护我们免受紫外线伤害的细胞从它们的起源开始，最终会变成潜在致命的癌症。 © 2023. Springer Nature Limited.

Over the past decade, melanoma has led the field in new cancer treatments, with impressive gains in on-treatment survival but more modest improvements in overall survival. Melanoma presents heterogeneity and transcriptional plasticity that recapitulates distinct melanocyte developmental states and phenotypes, allowing it to adapt to and eventually escape even the most advanced treatments. Despite remarkable advances in our understanding of melanoma biology and genetics, the melanoma cell of origin is still fiercely debated because both melanocyte stem cells and mature melanocytes can be transformed. Animal models and high-throughput single-cell sequencing approaches have opened new opportunities to address this question. Here, we discuss the melanocytic journey from the neural crest, where they emerge as melanoblasts, to the fully mature pigmented melanocytes resident in several tissues. We describe a new understanding of melanocyte biology and the different melanocyte subpopulations and microenvironments they inhabit, and how this provides unique insights into melanoma initiation and progression. We highlight recent findings on melanoma heterogeneity and transcriptional plasticity and their implications for exciting new research areas and treatment opportunities. The lessons from melanocyte biology reveal how cells that are present to protect us from the damaging effects of ultraviolet radiation reach back to their origins to become a potentially deadly cancer.© 2023. Springer Nature Limited.