Single‐Cell Transcription Reveals the Fibroblast Heterogeneity and Neural Cells' Significance in Desmoid Fibromatosis

ABSTRACT Desmoid fibromatosis (DF) is a refractory tumor with a high recurrence rate, resulting in severe organ's deformity, morbidity, and mortality. The cellular characteristics of DF remain elusive. Herein, we performed single‐cell RNA sequencing (scRNA‐seq) to reveal the cell landscape of DF. To uncover the exclusive characteristics of DF, we compared the transcriptional profile of DF with that of keloid fibroblast (KF) and normal fibroblast (NF) in the public data (GSE163973). When compared with KF and NF, mesenchymal fibroblasts were significantly expanded in DF. The mesenchymal fibroblasts were further divided into two subtypes according to the differentiation states, among which LAMP5 + SULF1 + fibroblasts may account for the hard property of DF by promoting tumor ossification. ADAM12 and CREB3L1 were identified as the specific marker and transcription factor for DF, respectively. Both the quiescent and proliferative COL11A1 + neural cells exerted dominant roles in the maintenance of the profibrotic microenvironment in DF through modulating extracellular matrix. This study revealed the heterogeneity of fibroblasts in DF for the first time. The novel gene markers and transcription factor identified in DF and the significance of neural cells in the tumor microenvironment may point to new directions for the targeted therapy of DF in the future.