Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis
- PMID: 32317643
- PMCID: PMC7174390
- DOI: 10.1038/s41467-020-15647-5
Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis
Abstract
Collagen-producing cells maintain the complex architecture of the lung and drive pathologic scarring in pulmonary fibrosis. Here we perform single-cell RNA-sequencing to identify all collagen-producing cells in normal and fibrotic lungs. We characterize multiple collagen-producing subpopulations with distinct anatomical localizations in different compartments of murine lungs. One subpopulation, characterized by expression of Cthrc1 (collagen triple helix repeat containing 1), emerges in fibrotic lungs and expresses the highest levels of collagens. Single-cell RNA-sequencing of human lungs, including those from idiopathic pulmonary fibrosis and scleroderma patients, demonstrate similar heterogeneity and CTHRC1-expressing fibroblasts present uniquely in fibrotic lungs. Immunostaining and in situ hybridization show that these cells are concentrated within fibroblastic foci. We purify collagen-producing subpopulations and find disease-relevant phenotypes of Cthrc1-expressing fibroblasts in in vitro and adoptive transfer experiments. Our atlas of collagen-producing cells provides a roadmap for studying the roles of these unique populations in homeostasis and pathologic fibrosis.
Conflict of interest statement
D.S. is a founder of Pliant Therapeutics and has received research funding from Abbvie, Pfizer and Pliant Therapeutics. He serves on the Scientific Review Board for Genentech, xCella Biosciences and Optikira. M.A.M. has received research funding from Bayer Therapeutics and is a consultant for Cerus Therapeutics and Gen1e Life Sciences. T.S.A., J.C.S., S.P., I.O.R., and N.K. are inventors on a provisional patent application (62/849,644), Yale University and Brigham and Women’s Hospital, Inc. that covers methods related to IPF associated cell subsets. N.K. served as a consultant to Biogen Idec, Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indaloo, Theravance, LifeMax, Three Lake Partners, Optikira over the last 3 years and received non-financial support from MiRagen.
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