Ontology highlight
ABSTRACT:
PROVIDER: PRJNA602744 | ENA |
REPOSITORIES: ENA
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Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease that is difficult to diagnose and follows an unpredictable clinical course. The object of this study was to develop a predictive gene signature model of IPF from whole lung tissue. We collected whole lung samples from 11 IPF patients undergoing diagnostic surgical biopsy or transplantation. Whenever possible, samples were obtained from different lobes. Normals consisted of healthy organs donated for transplantation. We measured gene expression on microarrays. Data were analyzed by hierarchical clustering and Principal Component Analysis. By this approach, we found that gene expression was similar in the upper and lower lobes of individuals with IPF. We also found that biopsied and explanted specimens contained different patterns of gene expression; therefore, we analyzed biopsies and explants separately. Signatures were derived by fitting top genes to a Bayesian probit regression model. We developed a 153-gene signature that discriminates IPF biopsies from normal. We also developed a 70-gene signature that discriminates IPF explants from normal. Both signatures were validated on an independent cohort. The IPF Biopsy signature correctly diagnosed 76% of the validation cases (p < 0.01), while IPF Explant correctly diagnosed 78% (p < 0.001). Examination of differentially expressed genes revealed partial overlap between IPF Biopsy and IPF Explant and almost no overlap with previously reported IPF gene lists. However, several overlapping genes may provide a basis for developing therapeutic targets. 17 samples from 11 patients with IPF (6 patients provided a pair of samples from upper and lower lobes; 5 patients contributed singleton samples); 6 control specimens were obtained from routine lung volume reduction of healthy donor lungs at the time of lung transplantation.
2011-11-01 | E-GEOD-24206 | biostudies-arrayexpress
Project description:Lung explant derived T cells were sorted from mechanically dissociated IPF lung explants and compared to CD4+ T cells magnetically sorted from the peripheral blood of normal donors.
2019-08-15 | GSE102751 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease that is difficult to diagnose and follows an unpredictable clinical course. The object of this study was to develop a predictive gene signature model of IPF from whole lung tissue. We collected whole lung samples from 11 IPF patients undergoing diagnostic surgical biopsy or transplantation. Whenever possible, samples were obtained from different lobes. Normals consisted of healthy organs donated for transplantation. We measured gene expression on microarrays. Data were analyzed by hierarchical clustering and Principal Component Analysis. By this approach, we found that gene expression was similar in the upper and lower lobes of individuals with IPF. We also found that biopsied and explanted specimens contained different patterns of gene expression; therefore, we analyzed biopsies and explants separately. Signatures were derived by fitting top genes to a Bayesian probit regression model. We developed a 153-gene signature that discriminates IPF biopsies from normal. We also developed a 70-gene signature that discriminates IPF explants from normal. Both signatures were validated on an independent cohort. The IPF Biopsy signature correctly diagnosed 76% of the validation cases (p < 0.01), while IPF Explant correctly diagnosed 78% (p < 0.001). Examination of differentially expressed genes revealed partial overlap between IPF Biopsy and IPF Explant and almost no overlap with previously reported IPF gene lists. However, several overlapping genes may provide a basis for developing therapeutic targets.
2011-11-01 | GSE24206 | GEO
Project description:Tissue fibrosis is a common pathological outcome of chronic disease that markedly impairs organ function leading to morbidity and mortality. In the lung, idiopathic pulmonary fibrosis (IPF) is an insidious and fatal interstitial lung disease associated with declining pulmonary function. Single cell RNA sequencing was used to map epithelial cell types of the normal human airway and alveolaor as well as IPF explant tissue.
2020-09-24 | GSE146981 | GEO
Project description:Mechanically dissociated IPF lung explant derived cellular suspensions were cultured in 50% senescent lung fibroblast conditioned medium + 50% fibroblast complete medium (DMEM + 15% FBS + antiboitics) and 10 µM of Y27632. After approximately 2 weeks, cells were passaged and cultured overnight in Pneumacult Ex Plus medium (STEMCELL technologies).
2018-09-04 | GSE115982 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is an irreversible diffuse parenchymal lung disease of poorly defined etiology. Patients with IPF frequently demonstrate distinctive lymphoplasmacellular infiltrations within remodeled lung tissue, the relevance of which in lung fibrogenesis is still understudied. Histopathological examination of explant lung tissue of patients with IPF revealed accentuated lymphoplasmacellular accumulates in close vicinity to or even infiltrating remodeled lung tissue. Similarly, we found significant accumulations of B cells interfused with T cells within remodeled lung tissue in two murine models of adenoviral TGF-β1 or bleomycin (BLM)-induced lung fibrosis. Such B cell accumulates coincided with significantly increased lung collagen deposition, lung histopathology and worsened lung function in WT mice. Importantly however, B cell deficient µMT KO mice responded similarly with lung tissue remodeling and worsened lung function upon either AdTGF-β1 or BLM treatment as did WT mice. Comparative transcriptomic profiling of sorted B cells collected from lungs of AdTGF-β1 and BLM exposed WT mice identified a large set of commonly regulated genes, however with significant enrichment observed for gene ontology terms (GO terms) apparently not related to lung fibrogenesis. Collectively, although we observed B cell accumulates in lungs of IPF patients as well as two experimental models of lung fibrosis, comparative profiling of characteristic features of lung fibrosis between WT and B cell-deficient mice did not support a major involvement of B cells in lung fibrogenesis in mice.
2021-12-29 | GSE180951 | GEO
Project description:Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an interstitial lung disease caused by sensitization to an inhaled allergen. Objectives: We aimed to identify the molecular determinants associated with progression of fibrosis. Methods: Nine fHP explant lungs and six unused donor lungs (as controls) were systematically sampled (4 samples/lung). According to microCT measures, fHP cores were clustered into a mild, moderate and severe fibrosis group. Gene expression profiles were assessed using Weighted Gene Co-expression Network Analysis (WGCNA), xCell, gene ontology and structure enrichment analysis. Gene expression of the prevailing molecular traits was also compared with IPF. The explant lung findings were evaluated in separate clinical fHP cohorts using tissue, bronchoalveolar lavage samples and computed tomography scans. Results: We found six molecular traits that associated with differential lung involvement. In fHP, extracellular matrix and antigen presentation/sensitization transcriptomic signatures characterized lung zones with only mild structural and histological changes, whereas signatures involved in honeycombing and B-cells dominated the transcriptome in the most severely affected lung zones. With increasing disease severity, endothelial function was progressively lost and progressive disruption in normal cellular homeostatic processes emerged. All six were also found in IPF, with largely similar associations with disease microenvironments. The molecular traits correlated with in vivo disease behaviour in a separate clinical fHP cohort. Conclusion: We identified six molecular traits which characterise the morphological progression of fHP and associate with in vivo clinical behaviour. Comparing IPF with fHP, the transcriptome landscape was determined considerably by local disease extent, rather than by diagnosis alone.
2022-01-01 | GSE184316 | GEO
Project description:We have performed single cell RNA sequencing on explant tissue of post-acute sequelae SARS-CoV-2 infection (PASC) patients. The study focused on epithelial cells (Epcam+) and immune cells (CD45+) cells. We further compared our PASC sample with Donor and IPF samples from GSE146981 and GSE135893.
2023-05-15 | GSE224955 | GEO
Project description:To further understand the pathologic microenvironment in IPF, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish normal and IPF lung in normal-looking, fibrotic foci and hyperplastic areas of IPF lung. Four IPF lungs were dissected into normal-looking, fibrotic foci and hyperplastic areas by Laser-Capture-Microdissection. Gene expression analysis showed that 638 significantly different genes were identified that clearly distinguished the different IPF microenvironments . Among them, MMP19 was revealed as one of the most significantly up-regulated genes that distinguished normal looking epithelial cells (N) to hyperplastic epithelial cells, MMP19 up-regulation in IPF lungs was verified by immunohistochemical (IHC), qRT-PCR and Western-blot. IPF lungs are heterogeneity complex, which comprise normal looking area, fibrotic foci and hyperplastic area. In this study we separated the normal, fibrotic foci and hyperplastic area by LCM and employed Agilent whole genome gene expression microarray profiling to identify genes with the potential to distinguish the unique microenironment of IPF
2013-01-11 | E-GEOD-35309 | biostudies-arrayexpress
Project description:Accelerated senescence in lung epithelial cells is known to play a key role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the exact mechanisms underlying the IPF-related epithelial cell phenotype have yet to be elucidated. Increasing evidence supports the concept that extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communication that contributes to diverse aspects of physiology and pathogenesis. Here, we demonstrate that lung fibroblasts (LFs) from IPF patients accelerate epithelial cell senescence via EV-mediated transfer of LF-derived pathogenic cargo to lung epithelial cells. Mechanistically, IPF LF-derived EVs increase mitochondrial reactive oxygen species (mtROS) and associated mitochondrial damage in lung epithelial cells, leading to mtROS-mediated activation of the DNA damage response and subsequent epithelial cell senescence. We show that IPF LF-derived EVs contain elevated levels of miR-23b-3p and miR-494-3p that are responsible for suppressing SIRT3, resulting in the EV-induced phenotypic changes of lung epithelial cells. Furthermore, we observe that miR-23b-3p and miR-494-3p expression increases in lung epithelial cells from IPF patients’ lungs. Finally, the levels of miR-23b-3p and 494-3p found in IPF LF-derived EVs correlate positively with IPF disease severity. These findings reveal that the accelerated epithelial cell mitochondrial damage and senescence observed during IPF pathogenesis are caused by a novel mechanism in which SIRT3 is suppressed by miR-containing EVs derived from IPF fibroblasts.
2020-08-04 | GSE124665 | GEO