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 (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.
Project description:Pulmonary fibrosis (PF) is associated with many chronic lung diseases including Systemic sclerosis (SSc), Idiopathic Pulmonary Fibrosis (IPF) and Cystic Fibrosis (CF) which are characterized by the progressive accumulation of mesenchymal cells and formation of scar tissue. Th2 T cell-derived cytokines including IL-4 and IL-13 have been shown to contribute to inflammation and fibrotic remodeling in multiple tissues. Interleukin-31 (IL-31) is a newly identified cytokine that is predominantly produced by CD4 Th2 T cells, but its signaling receptor IL-31RA is primarily expressed by non-hematopoietic cells. However, the potential role of the IL-31-IL31RA axis in pulmonary inflammation and fibrosis has remained largely unknown. To determine the role of IL-31 signaling in pulmonary fibrosis, wildtype, and IL-31RA knockout mice were treated with bleomycin and measured changes in total lung transcripts using RNA-seq. The total lung transcriptome analysis showed a significant reduction in fibrosis-associated gene transcripts including extracellular matrix and epithelial cell-associated gene networks.