Every cell in the human body has a unique set of somatic mutations, but it remains difficult to comprehensively genotype an individual cell 1 . Here we describe ways to overcome this obstacle in the context of normal human skin, thus offering a glimpse into the genomic landscapes of individual melanocytes from human skin. As expected, sun-shielded melanocytes had fewer mutations than sun-exposed melanocytes. However, melanocytes from chronically sun-exposed skin (for example, the face) had a lower mutation burden than melanocytes from intermittently sun-exposed skin (for example, the back). Melanocytes located adjacent to a skin cancer had higher mutation burdens than melanocytes from donors without skin cancer, implying that the mutation burden of normal skin can be used to measure cumulative sun damage and risk of skin cancer. Moreover, melanocytes from healthy skin commonly contained pathogenic mutations, although these mutations tended to be weakly oncogenic, probably explaining why they did not give rise to discernible lesions. Phylogenetic analyses identified groups of related melanocytes, suggesting that melanocytes spread throughout skin as fields of clonally related cells that are invisible to the naked eye. Overall, our results uncover the genomic landscapes of individual melanocytes, providing key insights into the causes and origins of melanoma. A combination of clonal expansion and DNA amplification is used to sequence genetic material from individual melanocytes, shedding light on the mutational landscape of these cells and the development of melanomas.

中文翻译：

---

人类皮肤中单个黑色素细胞的基因组图谱

人体中的每个细胞都有一组独特的体细胞突变，但仍然难以对单个细胞进行全面的基因分型 1 。在这里，我们描述了在正常人类皮肤的背景下克服这一障碍的方法，从而提供了对人类皮肤单个黑色素细胞基因组景观的一瞥。正如预期的那样，防晒黑素细胞的突变比暴露在阳光下的黑素细胞少。然而，来自长期暴露在阳光下的皮肤（例如，面部）的黑素细胞的突变负担低于来自间歇性暴露在阳光下的皮肤（例如，背部）的黑色素细胞。位于皮肤癌附近的黑色素细胞的突变负担高于来自没有皮肤癌的供体的黑色素细胞，这意味着正常皮肤的突变负担可用于衡量累积的阳光损伤和皮肤癌风险。而且，来自健康皮肤的黑素细胞通常含有致病突变，尽管这些突变往往是弱致癌性的，这可能解释了为什么它们没有引起可辨别的损伤。系统发育分析确定了相关的黑素细胞群，这表明黑素细胞作为肉眼不可见的克隆相关细胞场遍布整个皮肤。总体而言，我们的研究结果揭示了单个黑色素细胞的基因组图谱，为黑色素瘤的病因和起源提供了关键见解。克隆扩增和 DNA 扩增的组合用于对来自单个黑色素细胞的遗传物质进行测序，从而揭示这些细胞的突变景观和黑色素瘤的发展。可能解释了为什么它们没有引起明显的损伤。系统发育分析确定了相关的黑素细胞群，这表明黑素细胞作为肉眼不可见的克隆相关细胞场遍布整个皮肤。总体而言，我们的研究结果揭示了单个黑色素细胞的基因组图谱，为黑色素瘤的病因和起源提供了关键见解。克隆扩增和 DNA 扩增的组合用于对来自单个黑色素细胞的遗传物质进行测序，从而揭示这些细胞的突变景观和黑色素瘤的发展。可能解释了为什么它们没有引起明显的损伤。系统发育分析确定了相关的黑素细胞群，这表明黑素细胞作为肉眼不可见的克隆相关细胞场遍布整个皮肤。总体而言，我们的研究结果揭示了单个黑色素细胞的基因组图谱，为黑色素瘤的病因和起源提供了关键见解。克隆扩增和 DNA 扩增的组合用于对来自单个黑色素细胞的遗传物质进行测序，从而揭示这些细胞的突变景观和黑色素瘤的发展。这表明黑色素细胞作为肉眼不可见的克隆相关细胞场遍布整个皮肤。总体而言，我们的研究结果揭示了单个黑色素细胞的基因组图谱，为黑色素瘤的病因和起源提供了关键见解。克隆扩增和 DNA 扩增的组合用于对来自单个黑色素细胞的遗传物质进行测序，从而揭示这些细胞的突变景观和黑色素瘤的发展。这表明黑色素细胞作为肉眼不可见的克隆相关细胞场遍布整个皮肤。总体而言，我们的研究结果揭示了单个黑色素细胞的基因组图谱，为黑色素瘤的病因和起源提供了关键见解。克隆扩增和 DNA 扩增的组合用于对来自单个黑色素细胞的遗传物质进行测序，从而揭示这些细胞的突变景观和黑色素瘤的发展。