scRNA-seq reveals differences in cell states and cell types between human hip, palm, and sole skin. scRNA-seq reveals differences in cell states and cell types between human hip, palm, and sole skin

Palmoplantar skin is structurally and functionally unique, but the transcriptional programs driving this specialization are unknown. Here, we exploit 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 previously unappreciated differences between palmar and plantar sites. Our approach reveals downregulation of diverse immunological processes and decreased immune cell populations in palmoplantar skin, highlighting an altered immune environment in the skin of the palms and soles. Further, we identify specific palmoplantar and non-palmoplantar fibroblast populations that appear to orchestrate key differences in cell-cell communication in palm, sole, and hip. Dedicated analysis of epidermal keratinocytes highlights major differences in basal cell fraction among the three sites and validates the presence of a more differentiated, cycling basal population. Finally, our data demonstrate the existence of two spinous keratinocyte populations that constitute two parallel, site-selective epidermal differentiation trajectories. Together, these results provide a deep characterization of the highly adapted palmoplantar skin and contribute new insights into the fundamental biology of human skin. Overall design: scRNA-seq of skin biopsies from 4 healthy adult subjects; Subjects 1 and 2 were hip and sole matched, Subjects 3 and 4 were hip and palm matched

掌跖皮肤（palmoplantar skin）在结构与功能上均具有独特性，但驱动其特化的转录调控程序至今仍不明晰。本研究借助对人类手掌、足底及臀部皮肤的单细胞RNA测序（single-cell RNA-sequencing），阐明了掌跖皮肤与非掌跖皮肤的差异化特征，同时揭示了掌部与跖部皮肤此前未被重视的位点特异性差异。
本研究发现，掌跖皮肤中多种免疫相关生物学过程被下调，免疫细胞群体丰度显著降低，凸显掌部与足底皮肤的免疫微环境发生了重塑。此外，我们鉴定出专属的掌跖皮肤及非掌跖皮肤成纤维细胞亚群，这些亚群似乎主导了手掌、足底与臀部皮肤间细胞间通讯的核心差异。
针对表皮角质形成细胞的针对性分析显示，三个取样位点的基底细胞占比存在显著差异，并验证了一类更成熟、处于增殖状态的基底细胞群体的存在。最后，本研究数据证实存在两类棘层角质形成细胞亚群，它们构成两条平行的、位点特异性的表皮分化轨迹。
综上，本研究对高度特化的掌跖皮肤进行了深度表征，为人类皮肤的基础生物学研究提供了全新见解。
整体实验设计：对4名健康成人受试者的皮肤活检样本开展单细胞RNA测序；其中受试者1与2为臀部-足底配对样本，受试者3与4为臀部-手掌配对样本。