The goal of a new study published in Scientific Reports was to understand specific contributions of keratinocytes (KCs) to plaque formation. Here, RNA-seq was used to investigate the transcriptome of primary monolayer KC cultures grown from lesional (PP) and non-lesional (PN) biopsies of psoriasis patients and control subjects (NN). The results of the RNA-seq analysis of whole skin identified that a larger number of psoriasis-increased differentially expressed genes (DEGs), but analysis of KC cultures identified more PP- and PN-decreased DEGs. These latter DEG sets overlapped more strongly with genes near loci identified by psoriasis genome-wide association studies, and were enriched for genes associated with epidermal differentiation. Similarly, the frequency of activator protein (AP)-1 motifs was elevated in regions upstream of PN-KC-decreased DEGs. On the other hand, a subset of these genes belonged to the same co-expression module, mapped to the epidermal differentiation complex, and exhibited differentiation-dependent expression. The findings of this study demonstrated a decreased differentiation gene signature in PP/PN-KCs. It was stated that this may reflect intrinsic defects limiting psoriatic KC differentiation capacity, which may contribute to compromised barrier function in normal-appearing uninvolved psoriatic skin.¹

Reference

1. Swindell W, Sarkar M, Liang Y et al. RNA-seq identifies a diminished differentiation gene signature in primary monolayer keratinocytes grown from lesional and uninvolved psoriatic skin. Scientific Reports. 2017;7(1). doi:10.1038/s41598-017-18404-9.