Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA283423 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Experimental set 1: To evaluate the impact of apoptotic neutrophils on TLR4-induced inflammatory pathways in human macrophages. Experimental set 2: To compare the activation of inflammatory pathway between alveolar macrophages (AM) from idiopathic pulmonary fibrosis (IPF) patients and alveolar macrophages from respiratory bronchiolitis interstitial lung disease (RB-ILD) patients
2018-06-01 | GSE90010 | GEO
Project description:Aging is among the most important risk factors for the development of pulmonary fibrosis. Inappropriate or prolonged activation of the integrated stress response has been implicated in the pathobiology of both aging and pulmonary fibrosis. We found that a small molecule that relieves translational inhibition induced by activation of the integrated stress response (ISRIB) attenuated the severity pulmonary fibrosis in young and old mice. We demonstrate that severe fibrosis in old mice was associated with increased number of pathogenic monocyte-derived alveolar macrophages. Using transcriptomic profiling we found that ISRIB modulates stress response signaling in alveolar epithelial cells resulting in decreased recruitment of pathogenic monocyte-derived alveolar macrophages. Thus our data suggest that inhibition of the integrated stress response in the lung epithelium can ameliorate pulmonary fibrosis by preventing the recruitment of monocyte-derived alveolar macrophages.
2021-04-16 | GSE145771 | GEO
Project description:Aging is among the most important risk factors for the development of pulmonary fibrosis. Inappropriate or prolonged activation of the integrated stress response has been implicated in the pathobiology of both aging and pulmonary fibrosis. We found that a small molecule that relieves translational inhibition induced by activation of the integrated stress response (ISRIB) attenuated the severity pulmonary fibrosis in young and old mice. We demonstrate that severe fibrosis in old mice was associated with increased number of pathogenic monocyte-derived alveolar macrophages. Using transcriptomic profiling we found that ISRIB modulates stress response signaling in alveolar epithelial cells resulting in decreased recruitment of pathogenic monocyte-derived alveolar macrophages. Thus our data suggest that inhibition of the integrated stress response in the lung epithelium can ameliorate pulmonary fibrosis by preventing the recruitment of monocyte-derived alveolar macrophages.
2021-04-16 | GSE145295 | GEO
Project description:Aging is among the most important risk factors for the development of pulmonary fibrosis. Inappropriate or prolonged activation of the integrated stress response has been implicated in the pathobiology of both aging and pulmonary fibrosis. We found that a small molecule that relieves translational inhibition induced by activation of the integrated stress response (ISRIB) attenuated the severity pulmonary fibrosis in young and old mice. We demonstrate that severe fibrosis in old mice was associated with increased number of pathogenic monocyte-derived alveolar macrophages. Using transcriptomic profiling we found that ISRIB modulates stress response signaling in alveolar epithelial cells resulting in decreased recruitment of pathogenic monocyte-derived alveolar macrophages. Thus our data suggest that inhibition of the integrated stress response in the lung epithelium can ameliorate pulmonary fibrosis by preventing the recruitment of monocyte-derived alveolar macrophages.
2021-04-16 | GSE145590 | GEO
Project description:Alveoli are thin-walled sacs that serve as the gas exchange units of the lung. They are affected in devastating lung diseases including COPD, Idiopathic Pulmonary Fibrosis, and the major form (adenocarcinoma) of lung cancer, the leading cause of cancer deaths. The alveolar epithelium is composed of two morphologically distinct cell types: alveolar type (AT) 1 cells, exquisitely thin cells across which oxygen diffuses to reach the blood, and AT2 cells, specialized surfactant-secreting cells. Classical studies suggested that AT1 cells arise from AT2 cells during development and following injury, but more recent studies suggest other sources. Here we use histological and marker analysis, lineage tracing, and clonal analysis in mice to identify alveolar progenitor and stem cells and map their locations and potential in vivo. The results show that AT1 and AT2 cells arise independently during development from a bipotential progenitor. After birth, new AT1 cells derive from rare, long-lived, self-renewing AT2 cells, each producing a slowly expanding clonal focus of regenerated alveoli contiguous with the founder AT2 cell. This stem cell function of AT2 cells is broadly activated by diffuse AT1 cell injury, and AT2 self-renewal can be induced in vitro by EGF ligands and permanently activated in vivo by AT2 cell-specific targeting of the oncogenic KrasG12D allele, efficiently transforming AT2 cells into monoclonal adenomatous tumors that rapidly enlarge and prove fatal. Thus, there is a developmental switch in alveolar progenitor cells after birth, when mature AT2 cells function as facultative stem cells that contribute to local alveolar renewal, repair, and cancer. We propose that short-range signals from dying AT1 cells regulate AT2 stem cell activity: a signal transduced by EGFR-KRAS controls AT2 self-renewal and is hijacked during oncogenic transformation, and a separate signal controls reprogramming to AT1 cell fate. To compare expression between ATII and E18 BP populations, RNA was isolated from either population purified by FACS. Two populations are analyzed with 3 biological replicates per population.
2014-03-07 | E-GEOD-49346 | biostudies-arrayexpress
Project description:We developed an in vitro model of pulmonary fibrosis using alveolar organoids, consisting of human induced pluripotent stem cell-derived alveolar epithelial cells and human lung fibroblasts. In this model, fibroblasts were activated by bleomysin (BLM) treatment in an epithelial cell-dependent manner simillar to the pathogenic mechanism of pulmonary fibrosis.
2021-11-19 | GSE172121 | GEO
Project description:We developed an in vitro model of pulmonary fibrosis using alveolar organoids, consisting of human induced pluripotent stem cell-derived alveolar epithelial cells and human lung fibroblasts. In this model, fibroblasts were activated by bleomysin (BLM) treatment in an epithelial cell-dependent manner simillar to the pathogenic mechanism observed in pulmonary fibrosis.
2021-11-19 | GSE172122 | GEO
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>
| phs001750 | dbGaP
Project description:Chronic lung disease is increasing in prevalence and there is urgent need to advance our understanding of human lung biology in order to improve diagnosis and current treatments. The Th2 inflammatory cytokine Interleukin 13 (IL13) has been associated with both obstructive and fibrotic lung diseases, but its specific effect on the epithelial stem cells in the gas exchange compartment of the lung (alveolar space) has not been explored. Here, we use in vivo lung models of homeostasis and repair, ex vivo organoid platforms, and novel quantitative proteomic techniques to show that IL13 can directly disrupt the self-renewal and differentiation of both murine and human type 2 alveolar epithelial cells (AEC2s). We also show that IL13 promotes ectopic expression of markers typically associated with bronchiolar airway cells and commonly seen in the alveolar region of lung tissue from patients with idiopathic pulmonary fibrosis (IPF). Furthermore, we identify a number of proteins that are differentially secreted by AEC2s in response to IL13, suggesting that protein-based biomarkers may identify subsets of patients with pulmonary disease that is driven by “Th2-high” biology. This would allow us to understand some of the biological heterogeneity that exists in patients with chronic lung disease and to identify subsets of patients who may be more likely to respond to targeted anti-IL13 treatments.
2020-06-05 | PXD013006 | Pride