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<p>Here, to understand the homeostatic mechanisms governing melanocytes, we interrogate the mutational landscapes, gene-expression profiles and morphological features of 297 clonal expansions of epidermal melanocytes from 31 donors. We show that a population of melanocytes with low mutation burden persists in sun-exposed epidermis. These cells are smaller, less dendritic, and exhibit stem-like expression profiles when compared to melanocytes carrying high mutation burdens. Using single-cell spatial transcriptomics, we show that melanocytes inferred to have low mutation burdens localize to both hair follicles and interfollicular epidermis, whereas melanocytes with high mutation burdens are largely restricted to epidermis. We propose that melanocytes in the hair follicle occupy a privileged niche, protected from ultraviolet radiation, but replenish the epidermis following photodamage. This study highlights the value of incorporating mutational information into cell atlases. Cells can change their positions over time, but mutations provide a historical record of processes that were operative on each cell.</p>

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Somatic mutations distinguish melanocyte subpopulations in human skin

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月27日

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  • Bishal Tandukar,
  • Delahny Deivendran,
  • Limin Chen,
  • Neda Bahrani,
  • Defne Baskurt,
  • Beatrice Weier,
  • Harsh Sharma,
  • Noel Cruz-Pacheco,
  • Min Hu,
  • Kayla Marks,
  • Rebecca G. Zitnay,
  • Aravind K. Bandari,
  • Barbara Rentroia-Pacheco,
  • Rojina Nekoonam,
  • Boris C. Bastian,
  • Iwei Yeh,
  • Robert Judson-Torres,
  • A. Hunter Shain

摘要

Here, to understand the homeostatic mechanisms governing melanocytes, we interrogate the mutational landscapes, gene-expression profiles and morphological features of 297 clonal expansions of epidermal melanocytes from 31 donors. We show that a population of melanocytes with low mutation burden persists in sun-exposed epidermis. These cells are smaller, less dendritic, and exhibit stem-like expression profiles when compared to melanocytes carrying high mutation burdens. Using single-cell spatial transcriptomics, we show that melanocytes inferred to have low mutation burdens localize to both hair follicles and interfollicular epidermis, whereas melanocytes with high mutation burdens are largely restricted to epidermis. We propose that melanocytes in the hair follicle occupy a privileged niche, protected from ultraviolet radiation, but replenish the epidermis following photodamage. This study highlights the value of incorporating mutational information into cell atlases. Cells can change their positions over time, but mutations provide a historical record of processes that were operative on each cell.