1506 Multimodal transcriptomics highlight fibroblast heterogeneity and pathological signaling networks in keloid

Keloid, a tumor like scarring disorder, is caused by wounding in genetically predisposed individuals with poorly defined pathogenesis. To gain pathomechanistic details on keloid development, we performed single-cell RNA-sequencing and spatial transcriptomics edge adjacent non-lesional skin. Upon analysis, characterized ten major cell types based expression of known markers. Among those, fibroblasts significantly enriched at compared to the Further sub-clustering revealed three fibroblast subtypes, marked ASPN, CCL19, THSD4, respectively. Notably, ASPN+ CCL19+ consistently increased all patients were mutually markers human reticular dermal fibroblasts. Spatial mapping subtypes via RNAscope confirmed deep location their organization edge. Differential gene regulon analysis indicated that possessed many extracellular matrix inflammation related genes, driven uniquely active transcription factors. probe potential upstream signaling fibroblasts, cell-cell interaction neighboring cells, which abundant interactions specifically activated edge, including TGFb, CXCL, CCL pathways. Overall, our research suggested hyperproliferation may drive pathogenesis, partially producing excessive amounts promoting inflammation. These findings highlight role pathogenesis provide proof for targeting as an effective approach treatments.