328 Tyrosine hydroxylase-positive neurons boost fibroblast osteogenetic activity in keloid

Keloid is a common skin hyperplastic condition and paradigm of fibrotic disease. The cell interactions that underlie fibroblast hyperfunction, increased extracellular matrix stiffness, keloid formation remain elusive, which restricts the design preventative or interventional strategies with targeted purposes. Here we performed single-cell transcriptomic analysis on human unexpectedly found new cluster integrin binding sialoprotein (IBSP)-positive osteoblast-like cells were absent in normal skin. In situ RNA hybridization confirmed presence expressing IBSP skin, immunofluorescence further showed adjacency IBSP-secreting RUNX2+fibroblasts, whose number was transcriptome fibroblasts characterized by “response to catecholamine”, whole mount imaging intensive tyrosine hydroxylase (TH)-positive neurites release catecholamine as neurotransmitters. Fibroblasts from normal-looking margin exhibited expression RUNX2 IBSP, when treated neurotransmitters epinephrine norepinephrine. Accordingly, both hypersensitive stimulation than fibroblasts. Collectively, our data highlight neuron-stroma interaction promotes disposition stiff bone-constituting keloid.