Mesenchymal fibroblast cell promotes invasiveness of aggressive fibromatosis by remodeling extracellular matrix through CREB3L1/COL1A1 axis

Abstract

Background: Aggressive fibromatosis(AF) is an intermediate tumor originating from fibroblasts, but pathogenesis of which is not fully understood. Methods: We analyzed 53,203 single cells from thigh, neck, and forearm AF by using single-cell RNA sequencing integrates along with public single cell sequencing data of normal scars and keloids. We found an obvious increase in the population of mesenchymal fibroblasts in AF and proves the importance of this cell subsets in aggressive process by immunohistochemistry and multiple immunofluorescence. Results: We found that mesenchymal fibroblasts may modify the kinetics of extracellular matrix remodeling process of AF by changing the amount and type of collagen. Transcription factors that regulate mesenchymal fibroblast(MF) sub-clusters have been inferred by SCENIC regulons and we have identified CREB3L1/COL1A1 axis in MF clusters as potential transcriptional targets of AF and the mechanism of action may through relocation from cytoplasmic to cell nucleus. Conclusion : Mesenchymal fibroblast cell promotes invasiveness of aggressive fibromatosis by remodeling extracellular matrix through CREB3L1/COL1A1 axis. Our single cell sequencing results may provide detailed hints for clinical diagnosis and treatment for AF, and.