Differential cell composition and split epidermal differentiation in human palm, sole, and hip skin

Palmoplantar skin is structurally and functionally unique, but the transcriptional programs driving this specialization are unclear. Here, we use bulk and single-cell RNA sequencing of human palm, sole, and hip skin to describe the distinguishing characteristics of palmoplantar and non-palmoplantar skin while also uncovering differences between palmar and plantar sites. Our approach reveals an altered immune envi-ronment in palmoplantar skin, with downregulation of diverse immunological processes and decreased immune cell populations. Further, we identify specific fibroblast populations that appear to orchestrate key differences in cell-cell communication in palm, sole, and hip. Dedicated keratinocyte analysis highlights major differences in basal cell fraction among the three sites and demonstrates the existence of two spinous keratinocyte populations constituting parallel, site-selective epidermal differentiation trajectories. In summary, this deep characterization of highly adapted palmoplantar skin contributes key insights into the fundamental biology of human skin and provides a valuable data resource for further investigation.

Automated summary

By using bulk and single-cell RNA sequencing, this study reveals the distinguishing characteristics of palmoplantar and non-palmoplantar skin, as well as the differences between palmar and plantar sites. The study uncovers an altered immune environment in palmoplantar skin and identifies specific fibroblast populations that play key roles in cell-cell communication. It also highlights major differences in basal cell fraction among the three sites and demonstrates the existence of selective epidermal differentiation trajectories. Overall, this deep characterization of palmoplantar skin provides valuable insights into the fundamental biology of human skin.