Single Cell Analysis of Pulmonary Fibrosis

Pulmonary fibrosis is a heterogenous syndrome in which fibrotic scar replaces normal lung tissue. We performed massively parallel single-cell RNA-Seq on lung tissue from eight lung transplant donors and eight patients with pulmonary fibrosis. Combined with in situ RNA hybridization, with amplification, these data provide a molecular atlas of disease pathobiology. We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to non-overlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. Analysis of a cryobiopsy specimen from a patient with early disease supports the clinical application of single-cell RNA-Seq to develop personalized approaches to therapy.]]> Single-cell RNA-Seq was performed on eight donor lung biopsies and eight lung explants from patients with pulmonary fibrosis attributed to IPF (4 patients), systemic sclerosis (2 patients), polymyositis (1 patient) and chronic hypersensitivity pneumonitis (1 patient). All samples were obtained at the time of transplantation. Separately, we performed single-cell RNA-Seq using one bronchoscopic cryobiopsy sample from a patient subsequently diagnosed with IPF. Bulk RNA-Seq was performed on samples of lung biopsy tissue obtained from 14 donors prior to transplantation and 8 lung explants from transplant recipients with pulmonary fibrosis.]]>