Single-cell transcriptome analysis reveals keratinocyte subpopulations contributing to psoriasis in corneum and granular layer.

ABSTRACT

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease that is common and relapses easily. While the importance of keratinocyte proliferation in psoriasis development is well-documented, the specific functional subpopulations of epidermal keratinocytes associated with this disease remain enigmatic. MATERIALS AND METHODS: Therefore, in our analysis of single-cell transcriptome data from both normal and psoriatic skin tissues, we observed significant increases in certain keratinocytes in the stratum corneum (KC) and stratum granulosum (KG) within psoriatic skin. Furthermore, we identified upregulated expression of specific secreted factors known to promote inflammatory responses. Additionally, we conducted a KEGG pathway enrichment analysis on these identified subsets. RESULTS: In the stratum corneum, the expression of FTL was upregulated in HIST1H1C+ KC. S100P+ KC displayed a significant increase in the expression of both S100P and S100A10, whereas PRR9+ KC showed upregulated expression of DEFB4B, S100A8, and S100A12. SLURP1+ KC was characterized by elevated expression levels of IL-36G, SLURP1, and S100A12. Meanwhile, in the stratum granulosum, KRT1+ KG highly expressed SLURP1, S100A7, S100A8, and S100A9, while DEFB4B expression was upregulated in PI3+ KG. Our findings indicated that subsets within the stratum corneum primarily participate in pathways related to MAPK, NOD-like receptors, HIF-1, cell senescence, and other crucial processes. In contrast, subsets in the stratum granulosum were predominantly associated with pathways involving MAPK, NOD-like receptors, HIF-1, Hippo, mTOR, and IL-17. CONCLUSION: These findings not only uncover the keratinocyte subsets linked to psoriasis but also unveil the molecular mechanisms and related signaling pathways that drive psoriasis development. This knowledge opens new horizons for the development of innovative clinical treatment strategies for psoriasis.