Project description:<p>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.</p>
Project description:Pulmonary fibrosis is a heterogeneous 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. This dataset contains single-cell RNA-seq data generated from the lungs of the two naive mice, human data for this study has been submitted to dbGap/SRA.
Project description:Pulmonary fibrosis is a heterogeneous 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.
Project description:Pulmonary fibrosis (PF) is an intractable disorder with a poor prognosis. Although multiple cell subsets contribute to the pathogenesis of PF, the entiety of the changes of cell-cell interaction remain unclear. To identify PF pathology-associated changes in cell-cell interaction network, we performed time-course single-cell transcriptome analysis of the single cell suspensiton obtained from the lungs of bleomycin-treated mice.
Project description:Pulmonary fibrosis is a progressive interstitial lung disease characterised by a progressive loss of lung function. It can occur as a result of occupational or medical exposures, genetic defects, trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can occur in an idiopathic manner. The pathogenesis of each form of pulmonary fibrosis remains unclear. A variety of animal models have been developed to better understand the pathogenesis of pulmonary fibrosis. It has been shown that animal models of pulmonary fibrosis rely heavily on severe adverse effects induced by a variety of drugs, such as bleomycin, amiodarone, lipopolysaccharide and silica. The construction of animal models plays a key role in our understanding of the molecular mechanisms underlying the pathogenesis of PF, in outlining patient-specific pathology and in developing therapeutic strategies. However, the differences between models of pulmonary fibrosis induced by different drugs have rarely been investigated. Therefore, in this paper we performed single-cell sequencing analysis of animal models constructed from four drugs. The characteristics of the changes in the number of epithelial cells and macrophages and their functional enrichment in each model were summarised, and it was deduced that the model induced by lipopolysaccharide was mainly focused on the inflammatory damage stage of pulmonary fibrosis, the model induced by amiodarone on the regeneration stage of persistent failure, and the model induced by bleomycin and silica on the fibrotic stage of pulmonary fibrosis.
Project description:Pulmonary fibrosis (PF) is a form of chronic lung disease characterized by progressive destruction of normal alveolar gas-exchange surfaces and accumulation of extracellular matrix (ECM). In order to comprehensively define the cell types, mechanisms and mediators driving ECM deposition and fibrotic remodeling in lungs with pulmonary fibrosis, we performed single-cell RNA-sequencing (scRNA-seq) of single-cell suspensions generated from non-fibrotic control and PF lungs. Analysis of over 114,000 cells from 20 PF and 10 control lungs identified 31 distinct cell types. We identified multiple distinct lineages directly contribute to ECM expansion, including a novel HAS1hi fibroblast subtype and a previously undescribed KRT5-/KRT17+, collagen and ECM-producing epithelial cell population that was highly enriched in PF lungs. Together these data provide high-resolution insights into the basic mechanisms of pulmonary fibrosis, and indicate a direct profibrotic role of the lung epithelium in PF pathogenesis.