Profiling Long Noncoding RNA in Psoriatic Skin Using Single-Cell RNA Sequencing

The expressions of long noncoding RNAs (lncRNAs) and their roles in epidermal differentiation have been previously defined using bulk RNA sequencing. Despite their tissue-specific expression profiles, most lncRNAs are not well-annotated at the single-cell level. In this study, we evaluated the use of single-cell RNA sequencing to profile and characterize lncRNAs using data from 6 patients with psoriasis with paired uninvolved and lesional psoriatic skin. Despite their overall lower expression, we were able to detect >7000 skin-expressing lncRNAs and their cellular sources. Differential gene expression analysis revealed 137 differentially expressed lncRNAs in lesional psoriasis skin and identified 169 cell-type-specific lncRNAs. Keratinocytes had the highest number of differentially expressed lncRNA in psoriatic skin, which we validated using spatial transcriptomic data. We further showed that expression of the keratinocyte-specific lncRNA, AC020916.1, upregulated in lesional skin, is significantly correlated with expressions of genes participating in cell proliferation/epidermal differentiation, including SPRR2E and transcription factor ZFP36, particularly in the psoriatic skin. Our study highlights the potential for using single-cell RNA sequencing to profile skin-expressing lncRNA transcripts and to infer their cellular origins, providing a crucial approach that can be applied to the study of other inflammatory skin conditions.