Human induced pluripotent stem cell-derived skin organoids recapitulate donor-specific pigmentation diversity

To address this, we employ a recently developed skin organoid (SkO) culture system that bioengineers nearly complete skin, including hair follicles and pigmentation, from human pluripotent stem cells. In this study, we generate SkOs from a panel of iPSC lines derived from donors with varying skin tones – light- and dark-pigmented.

By modulating TGFβ, BMP4, and FGF signaling pathways during early differentiation, followed by 4–5 months in floating culture, we generated SkOs. Through immunostaining and transmission electron microscopy, we observed distinct pigmentation patterns and differences in melanin production in both the skin and hair follicles of organoids derived from different donor lines. We further perform single-cell RNA sequencing to uncover gene expression profiles associated with these pigmentation differences.