Open AccessA vasculature niche orchestrates stromal cell phenotype through PDGF signaling: Importance in human fibrotic disease
Author(s) -
T. B. Layton,
Lynn M. Williams,
Nan Yang,
Mingjun Zhang,
Carl Lee,
Marc Feldmann,
Glenda Trujillo,
Dominic Furniss,
Jagdeep Nanchahal
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2120336119
Subject(s) - myofibroblast , stromal cell , biology , pericyte , phenotype , fibrosis , mesenchymal stem cell , population , pathology , microbiology and biotechnology , cell , cancer research , endothelial stem cell , medicine , genetics , gene , environmental health , in vitro
Significance Tissue fibrotic diseases, for example of the liver and lung, represent a huge unmet medical need. In this study, using single-cell RNA sequencing, cytometry by time of flight (CyTOF), tissue imaging, and functional assays, we identify a complex vascular niche in Dupuytren’s disease (DD), a common localized fibrotic condition of the palm, where early-disease-stage tissue can be accessed readily. We uncover a population of myofibroblast precursors within the pericyte compartment and demonstrate that the endothelium instructs the differentiation of functionally distinct stromal cells, thereby orchestrating discrete microenvironments in the fibrotic milieu. Together, these findings provide a basis for the concept of targeting blood vessel signaling to control the progression of human fibrosis.