The transcriptional profile of keloidal Schwann cells

Abstract

Recently, a specific Schwann cell type with profibrotic and tissue regenerative properties that contributes to keloid formation has been identified. In the present study, we reanalyzed published single-cell RNA sequencing (scRNA-seq) studies of keloids, healthy skin, and normal scars to reliably determine the specific gene expression profile of keloid-specific Schwann cell types in more detail. We were able to confirm the presence of the repair-like, profibrotic Schwann cell type in the datasets of all three studies and identified a specific gene-set for these Schwann cells. In contrast to keloids, in normal scars, the number of Schwann cells was not increased, nor was their gene expression profile distinctly different from that of Schwann cells of normal skin. In addition, our bioinformatics analysis provided evidence for a role of transcription factors of the AP1, STAT, and KLF families, and members of the IER genes in the dedifferentiation process of keloidal Schwann cells. Together, our analysis strengthens the role of the profibrotic Schwann cell type in the formation of keloids. Knowledge of the exact gene expression profile of these Schwann cells will facilitate their identification in other organs and diseases.

Transcriptional profiling sheds light on the fibrotic aspects of idiopathic subglottic tracheal stenosis

“…In keloids, SCs exist in an activated state, promoting synthesis of extracellular matrix (20). In our study, we detected the presence of SCs in ISGS with a specific gene expression pattern indicative of cell activation, featuring genes such as IGFBP5 and CCN3 , which are characteristic for pro-fibrotic SCs (21). Additionally, these SCs expressed EGFL8 , a gene secreted by repair-related SCs, implicated in neurite growth and neuronal differentiation (50).…”

“…Interestingly, we also detected genes such as EGFL8 and CDH19 , which are known marker genes of SC precursors and repair SCs (Figure 4E) (41, 42). Recently, we identified the transcriptional pattern of profibrotic Schwann cells in pathologic scars (21).…”

“…All subset analyses were performed based on the raw data of the selected cell cluster. Subtype characterization was conducted using published subtype clustermarker (21, 29). The subtype annotation of plasma cells according to published subtype marker genes was not sufficient, therefore a consecutive numbering of the clusters was chosen.…”

“…Beyond the well-established role of fibroblasts, recent discoveries have highlighted the involvement of Schwann cells in fibrotic processes (19, 20). These profibrotic Schwann cells exhibit a specific molecular pattern, contributing the matrix formation and influence other cell types, particularly macrophages (20, 21).…”

Skin fibroblast functional heterogeneity in health and disease

“…Fibroblast heterogeneity in localised skin fibrotic lesions has been explored in several recent single-cell RNA-seq studies, in particular in keloid scars [23,64,65]. Comparing keloid scar tissue to normal scar identified five major fibroblast clusters and mapped the four functional fibroblast subsets (secretory-papillary, secretory-reticular, mesenchymal, and pro-inflammatory fibroblasts) observed in healthy human skin [11,23] (Figure 1).…”