Project description:The libraries contained in this experiment come from lung fibroblasts primary nuclear extracts, IMR90. They are stranded PE101 Illumina Hi-Seq RNA-Seq libraries from rRNA-depleted Poly-A+ RNA > 200 nucleotides in size. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Project description:Primary lung fibroblast were isolated from well-matched control donors (no COPD, n=3) and patients with COPD (GOLD stage I-IV, n=8). Total RNA of cultured human lung fibroblast were isolated at passage 3 and rRNA was depleted. 75 bp single-end reads were generated from RNA libraries on Illumina NextSeq 500.
Project description:Our preliminary data show that the primary triple-negative breast tumor-derived chemokines CXCL1/2/8 promote migration and tube formation of mouse lung endothelial cells, which is mediated by lung fibroblasts. To explore the molecular events underlying this mediator function of lung fibroblasts, we treated freshly-isolated lung fibroblasts with chemokines CXCL1/2/8 and performed RNA-Seq assay.
Project description:We found that JUN expression is increased in many human fibrotic diseases and that systemic induction of Jun in mice resulted in development of fibrosis of multiple organs. To identify the changes in chromatin accessibility associated with JUN, we worked with primary human fibrotic lung fibroblasts that have normal or Knock-out levels of JUN expression and performed ATAC-seq analysis in both of them. Meanwhile we also modified primary human normal lung fibroblasts with or without JUN over-expression induction, then processed ATAC-seq and ChIP-seq analysis.
Project description:Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic lung disease with a median survival of 2-4 years. Injury to and/or dysfunction of alveolar epithelium are strongly implicated in IPF disease initiation, but what factors determine why fibrosis progresses rather than normal tissue repair occurs remain poorly understood. We previously demonstrated that ZEB1-mediated epithelial-mesenchymal transition (EMT) in human alveolar epithelial type II (ATII) cells augments TGF-β-induced profibrogenic responses in underlying lung fibroblasts by paracrine signalling. Here we investigated bi-directional epithelial-mesenchymal crosstalk and its potential to drive fibrosis progression. RNA sequencing (RNA-seq) of lung fibroblasts exposed to conditioned media from ATII cells undergoing RAS-induced EMT identified many differentially expressed genes including those involved in cell migration and extracellular matrix (ECM) regulation. We confirmed that paracrine signalling between AS-activated ATII cells and fibroblasts augmented fibroblast recruitment and demonstrated that this involved a ZEB1-tissue plasminogen activator (tPA) axis. In a reciprocal fashion, paracrine signalling from TGF-β-activated lung fibroblasts or IPF fibroblasts induced RAS activation in ATII cells, at least partially via the secreted protein, SPARC. Together these data identify that aberrant bi-directional epithelial-mesenchymal crosstalk in IPF drives a chronic feedback loop that maintains a wound-healing phenotype and provides self-sustaining pro-fibrotic signals.