Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1221872 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32295404_1.fastq.gz | Fastqsanger.gz | |||
| SRR32295404_2.fastq.gz | Fastqsanger.gz |
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Project description:Investigate profibrotic regulators contributing to epithelial-mesenchymal transformation and the pathogenesis of pulmonary fibrosis.
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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>
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Project description:Invasive lung myofibroblasts are the main cause of tissue remodeling in idiopathic pulmonary fibrosis (IPF). A key mechanism contributing to this important feature is aberrant crosstalk between the abnormal/injured lung epithelium and pulmonary fibroblasts. Here, we demonstrated that lungs from patients with IPF and from mice with bleomycin (BLM)-induced pulmonary fibrosis (PF) are characterized by the induction of human epididymis protein 4 (HE4) overexpression in epithelial cells. HE4 knockdown primarily in epithelial cells attenuated BLM-induced PF in mice, whereas the administration of recombinant mouse HE4 exacerbated fibrosis after BLM stimulation. Mechanistic analysis showed that HE4 and annexin II (ANXA2) specific binding enhanced the profibrotic phenotype in epithelial cells, and directly promoted lung fibroblast activation, leading to aberrant epithelial-fibroblast crosstalk and the persistent myofibroblast phenotype. The HE4 and ANXA2 binding site was located after the 30th amino acid at the N terminus of the HE4 molecule. Finally, intratracheal administration of HE4 shRNA lentivirus protected mice against BLM-induced PF. These data suggest that HE4 can serve as a novel therapeutic target in the treatment of IPF.
2024-12-17 | PXD058959 |
Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal pulmonary disorder characterized by fibroblast proliferation and the excess deposit of extracellular matrix proteins. The etiology of IPF is unknown, but a central role for microRNAs (miRNAs), a class of small non-coding regulatory RNAs, has been recently suggested. We report the upregulation of miR-199a-5p in mouse lungs undergoing bleomycin-induced fibrosis and also in human biopsies from IPF patients. Levels of miR-199a-5p were increased selectively in myofibroblasts and putative profibrotic effects of miR-199a-5p were further investigated in cultured lung fibroblasts. MiR-199a-5p expression was induced upon TGFβ exposure and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts. CAV1, a critical mediator of pulmonary fibrosis, was established as a bona fide target of miR-199a-5p. Finally, we also found an aberrant expression of miR-199a-5p in mouse models of kidney and liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. We propose miR-199a-5p as a major regulator of fibrosis that represents a potential therapeutic target to treat fibroproliferative diseases. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-02-01 | E-GEOD-34818 | biostudies-arrayexpress
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. Pulmonary fibrosis is a dysregulated response to alveolar injury which causes a progressive decline in lung function and refractory to current pharmacological therapies. Airway and alveolar epithelial cells and mesenchymal cells contribute to pulmonary fibrosis but the cell-specific pathways and gene networks that are responsible for the pathophysiology are unknown. Our new findings have identified the aberrant activation of Sox9 in lung resident fibroblasts and myofibroblasts in IPF lung biopsies and the mouse model of transforming growth factor-α (TGFα) and bleomycin-induced pulmonary fibrosis. In this study, we sought to determine Sox9-driven gene networks in lung resident fibroblast during pulmonary fibrosis. Our results showed that Sox9 regulates the transcriptional changes that are required for the fibroblast activation including migration, myofibroblast transformation, survival and extracellular matrix deposition during pulmonary fibrosis. In summary, this new study demonstrates that Sox9 is a critical regulator of fibroblast activation in IPF and hence serve as a target for therapeutic intervention.
2021-12-31 | GSE171532 | GEO
Project description:Single-cell RNA-sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis
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Project description:The interaction of lung epithelial and lung mesenchymal cells was investigated in a novel co-culture model of human pulmonary fibrosis. Remarkably, co-culturing both cell types induced cell-type-specific responses, including fibroblast-to-myofibroblast differentiation and epithelial-to-mesenchymal transition (EMT), which were fully dependent on direct epithelial / fibroblast contact. We used single-cell RNA sequencing (scRNA-seq) to evaluate the transcriptional fate of the normal human lung fibroblasts (NHLF) and normal human bronchiolar epithelial cells (NHBE) during the course of co-cultivation, and compare the single cell profiles with their counterpart isolated from patients with idiopathic pulmonary fibrosis (IPF). NHLF and normal NHBE cells were grown as co-cultures, cell suspensions were collected at the time points t = 0h, 3h and 18h and analyzed by single-cell RNA-seq on a Chromium Platform. Eight samples were sequenced, resulting in a total of xx single cell transcription profiles.
2022-10-03 | E-MTAB-11847 | biostudies-arrayexpress
Project description:The successful repair of alveolar epithelial injury is required to restore the integrity of gas exchanging regions of the lung and preserve organ function. Severe pulmonary fibrosis is the result of repeated episodes of epithelial injury, activation of fibroblasts, and matrix accumulation. Thus, impaired alveolar epithelial progenitor cell renewal could contribute to the progression of fibrosis. We provide evidence that expression of TLR4 and hyaluronan (HA) on Type 2 alveolar epithelial cells (AEC2s) is necessary for self-renewal. Either deletion of TLR4 or HA synthase 2 leads to impaired regeneration of AEC2s, severe fibrosis and mortality, in part due to blunted production of IL-6. AEC2s from patients with pulmonary fibrosis have reduced cell surface HA, and impaired renewal capacity, suggesting that interactions between HA and TLR4 are key regulators of lung stem cell renewal, repair of lung injury and that severe pulmonary fibrosis is the result of epithelial stem cell failure. We used microarrays to detail the gene expression of AEC2 cells from WT and TLR4-/- mice.
2016-10-03 | GSE68704 | GEO
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.
2018-12-15 | GSE122960 | GEO
Project description:The clinical course of SARS-CoV-2 infection is highly variable with a subset of patients developing severe COVID-19 and acute respiratory distress syndrome (ARDS). COVID-19 induced lung injury and respiratory failure appears to be driven by dysregulated immune responses, yet the exact mechanisms remain unknown. Here, we analyzed monocytes isolated from healthy donors treated with SARS-CoV-2, influenza A (Panama strain) or TLR7/8 agonist R848. Notably, overnight exposure to SARS-CoV-2, but not influenza A virus, induced a profibrotic signature, characterized by high expression of known fibrogenic factors like TGFB1, SPP1 and LGMN, and showed highly significant similarity with profibrotic macrophage populations identified in idiopathic pulmonary fibrosis (IPF). In conclusion, SARS-CoV-2 triggers profibrotic macrophage responses, and ARDS-associated lung fibrosis.
2021-11-29 | PXD022709 | Pride