Keloid transcriptomics reveal heterogeneity in fibroblast subtype enrichment, gene expression, and immune cell responses

Keloid disease, a skin disorder characterized by abnormal scar formation, leads to pain, itching and decreased quality of life for those affected. Despite numerous transcriptomic studies on this condition, the impact of cell type composition on overall gene expression in bulk tissue remains unclear. To address this knowledge gap, researchers analyzed the fibroblast subtype and immune cell enrichment in head and neck keloid tissue and matched adjacent normal skin tissue from 14 patients, comprising 10 African American and 4 European American individuals.

By employing single sample gene set enrichment analysis, the team determined cell type enrichment across both tissue samples. Linear mixed-effects models were applied to explore 1) differential cell type enrichment across tissue, 2) tissue-specific associations between fibroblast subtypes and immune cells, and 3) differentially expressed genes across tissue. To verify these findings, the research was replicated in an independent cohort of 8 African Americans.

The study uncovered three fibroblast subtypes and 14 immune cell types that were differentially enriched in the keloid tissue compared to the matched normal skin tissue. Furthermore, 17 tissue-specific associations between fibroblast subtypes and immune cells were identified, with 14 of these associations showing decreased expression in keloid tissue relative to the matched normal skin tissue.

After accounting for cell type enrichment, the researchers identified two significant differentially expressed genes, MIR31HG with a large positive fold-change and NR4A2 with a substantial negative fold-change.

By considering the cell type enrichment, this study reveals underlying tissue-specific associations between cell types and gene expression in keloid tissue, providing valuable insights into the heterogeneity of this condition.