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Single-cell RNA-seq reveals keratinocyte and fibroblast heterogeneity and their crosstalk via epithelial-mesenchymal transition in psoriasis

Dianhao Guo, Xiaokang Li, Jing Wang, Xin Liu, Yibo Wang, Shuhong Huang, Ningning Dang

2024Cell Death and Disease28 citationsDOIOpen Access PDF

Abstract

The pathogenesis of psoriasis, a chronic inflammatory autoimmune skin disease with a high global prevalence, remains unclear. We performed a high-resolution single-cell RNA sequencing analysis of 94,759 cells from 13 samples, including those from psoriasis model mice and wild-type mice. We presented a single-cell atlas of the skin of imiquimod-induced mice with psoriasis and WT mice, especially the heterogeneity of keratinocytes and fibroblasts. More interestingly, we discovered that special keratinocyte subtypes and fibroblast subtypes could interact with each other through epithelial-mesenchymal transition and validated the results with drug verification. Moreover, we conducted a tentative exploration of the potential pathways involved and revealed that the IL-17 signalling pathway may be the most relevant pathway. Collectively, we revealed the full-cycle landscape of key cells associated with psoriasis and provided a more comprehensive understanding of the pathogenesis of psoriasis.

Topics & Concepts

PsoriasisPathogenesisKeratinocyteCrosstalkEpithelial–mesenchymal transitionFibroblastMesenchymal stem cellBiologyImiquimodCancer researchCellImmunologyCell biologyTransition (genetics)Cell cultureGeneticsGeneOpticsPhysicsT-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisSingle-cell and spatial transcriptomics
Single-cell RNA-seq reveals keratinocyte and fibroblast heterogeneity and their crosstalk via epithelial-mesenchymal transition in psoriasis | Litcius