The genomic landscapes of individual melanocytes from human skin

Every cell in the human body has a unique set of somatic mutations, but it remains difficult to comprehensively genotype an individual cell . 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 melanoc...

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Bibliographic Details
Published in:	Nature (London) 2020-10, Vol.586 (7830), p.600-605
Main Authors:	Tang, Jessica, Fewings, Eleanor, Chang, Darwin, Zeng, Hanlin, Liu, Shanshan, Jorapur, Aparna, Belote, Rachel L, McNeal, Andrew S, Tan, Tuyet M, Yeh, Iwei, Arron, Sarah T, Judson-Torres, Robert L, Bastian, Boris C, Shain, A Hunter
Format:	Article
Language:	eng
Subjects:	Cancer Deoxyribonucleic acid Development and progression DNA DNA Mutational Analysis Exposure Female Genetic aspects Genome, Human - genetics Genomes Genomics Genotype Genotype & phenotype Genotypes Haplotypes Health Health risks Humans Male Melanocytes Melanocytes - cytology Melanocytes - metabolism Melanocytes - pathology Melanoma Melanoma - genetics Melanoma - pathology Mutation Phylogeny Physiological aspects Single-Cell Analysis Skin Skin - cytology Skin - pathology Skin cancer Skin diseases Sun Ultraviolet radiation Workflow
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Summary:	Every cell in the human body has a unique set of somatic mutations, but it remains difficult to comprehensively genotype an individual cell . 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.
ISSN:	0028-0836 1476-4687