Single-Cell Transcriptomics Reveals RNA-Binding Protein-Associated Cellular Heterogeneity and Regulatory Networks in Psoriatic Skin

Background: T cell differentiation, aberrant keratinocyte proliferation, and immune cell infiltration are the hallmarks of psoriasis, a chronic inflammatory skin condition. The expression patterns of RNA-binding proteins (RBPs), which are important post-transcriptional regulators of gene expression, in psoriatic skin remain largely unexplored. Dysregulation of RBPs has been implicated in the pathogenesis of various illnesses.Methods: In order to describe cellular composition, RBP expression heterogeneity, and intercellular communication networks, we methodically examined single-cell RNA sequencing (RNA-seq) data in this work. To identify RBP expression subgroups across various cell types, such as keratinocytes, dendritic cells, and T cells, 2141 known RBP genes were utilized for unsupervised clustering. RBP-associated functional pathways were found using Gene Ontology (GO) enrichment and co-expression network analysis. Cell-to-cell communication was examined using CellChat analysis. Additionally, RBP-associated alternative splicing events in psoriasis were assessed by integrating bulk RNA-seq data.Results: When compared to healthy skin, psoriatic skin showed higher percentages of T cells and dendritic cells and lower percentages of keratinocytes. Different disease-associated RBP expression subgroups were identified by RBP-based clustering, particularly in keratinocytes, dendritic cells, and T cells. Differentially expressed RBPs were shown to be primarily involved in keratinocyte differentiation, immunological responses, antigen processing and presentation, inflammation, and apoptosis, according to functional studies. Significantly increased interactions between keratinocytes and immune cells in psoriasis were revealed by cell-cell communication analysis. These interactions involved important signaling pathways like major histocompatibility complex (MHC)-I/II, macrophage migration inhibitory factor (MIF), C-C motif chemokine ligand (CCL), and cluster of differentiation 99 (CD99). Additionally, integration with bulk RNA-seq data showed extensive alternative splicing changes in psoriatic skin, which were closely associated with dysregulated RBP expression.Conclusion: Through controlling keratinocyte function and immune cell activation, RBPs may contribute to the etiology of psoriasis. This study offers a comprehensive characterization of RBP expression across several cell types in psoriatic skin.