BAL cell gene expression is predictive of Mortality in Idiopathic Pulmonary Fibrosis and enriched for Genes of Airway Basal Cells (III)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE73394 | GEO | 2018/12/31
REPOSITORIES: GEO
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Project description:Background: We got interested whether genes of airway basal cells are enriched in COPD. Methods: Bronchoscopy with bronchial brushes and bronchoalveolar lavage was performed in 28 patients with COPD and 29 healthy donors and isolated BAL cells.Transcriptome of BAL cells were studied by using Affymetrix Human Genome U133 Plus 2.0 array on an Affymetrix platform. Microarray data were normalized data were imported, log2-transformed and quantile normalized using robust multi-array average (RMA). We tested enrichment for airway basal cells by ROMER enrichment analysis. Results: we did not find enrichment of airway basal cell genes in COPD compared to healthy volunteers.
2018-12-31 | GSE73395 | GEO
Project description:Introduction: Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in alveolar macrophagesâa key immuno-inflammatory cell in the lungâcan shed light on the pathogenesis of this complex disease. Methods: We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from bronchoalveolar (BAL) cells and hybridized to an Affymetrix GeneChip Human Genome U133A 2.0 microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these groups, we applied gene set enrichment analysis (GSEA) to the transcriptional profiles of BAL cells. We used false discovery rate (FDR) < 0.01 to designate significant enrichment. Results: Sarcoid patients were either non-smokers or ex-smokers, all had lung involvement and only 2 were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression between sarcoidosis and healthy subjects revealed over 1200 differentially expressed genes at an FDR cutoff < 0.01. Several previously described immune mediators, such as interferon gamma, were up-regulated in the sarcoidosis subjects. Since genes often exert their influence through functionally coherent modules, we performed GSEA based on global expression profiles of alveolar macrophages between the subject groups. We identified more than 200 gene sets enriched in patients with sarcoidosis whereas very few pathways were over-represented in the healthy controls. Many of the sarcoidosis-associated pathways mapped to inflammatory and immune-related processes including T-cell signaling, graft vs. host disease, IL-12, IL-23, and IL-17 pathways, and oxidative phosphorylation. However, we also found and confirmed significant alteration in Proteasome-related pathways. Conclusions: BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional networks involved in immuno-inflammatory and proteasomal processes. Our findings add to the growing evidence implicating airspace resident cells in the pathogenesis of sarcoidoisis and identify specific pathways whose activation may modulate disease progression. Total RNA from BAL cells of 15 subjects with sarcoidosis and 12 healthy controls was hybridized to 27 Affymetrix Genechip Human U133A 2.0 microarrays
2016-07-22 | E-GEOD-75023 | biostudies-arrayexpress
Project description:Background: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with variable outcome. Currently, there is little information whether changes in molecular pathways in the alveolar compartment of patients with IPF are indicative of disease progression. To address this question we analyzed gene expression signatures in cells obtained from bronchoalveolar lavage (BAL) of patients with IPF. Methods: BAL cells were harvested from 212 IPF patients and 20 healthy donors at the time of diagnosis. RNA was extracted, labeled and hybridized to Agilent gene expression arrays. Our study included a discovery cohort of 62 patients from Freiburg, Germany, and two independent validation cohorts, Siena, Italy (50 patients) and Leuven, Belgium (64 patients). Survival analysis was performed by applying Cox models and component-wise boosting. Results: We found 1582 genes predictive of mortality in the discovery cohort in univariate analyses adjusted for age and gender at FDR<0.05. A nine gene signature, developed by component-wise boosting in the Freiburg array dataset, performed well in both validation cohorts, Siena (p<0.0032) and Leuven (p=0.0033). The genes associated with mortality in BAL cells were significantly enriched for genes expressed in airway basal epithelial cells, airway progenitor cells recently implicated in fibrosis. Conclusions: Our results identify and validate a BAL cell gene expression signature that predicts mortality in IPF. This signature unmasks a potential novel role for airway basal epithelial cells in IPF.
2018-12-31 | GSE70866 | GEO
Project description:Lung tissue from fetal and neonatal lung samples is tough to obtain, and capturing cells from a living patient with evolving or established disease is very challenging. We hypothesized that airway organoids derived from BAL samples from intubated preterm neonates with established BPD will recapitulate the epithelial heterogeneity seen in human airways and can be used for studying injury and therapy responses in vitro. BPD patient BAL-derived airway organoids exhibited cellular heterogeneity consistent with that observed in the human airway. BAL sample-derived airway organoids from patients with established BPD contain basal cell progenitors and a spectrum of differentiated epithelial subtypes, including secretory, ciliated, PNECs, and hillock cells. Hyperoxia exposure and treatment with dexamethasone caused significant cellular transcriptional changes and highlighted biological pathways, both known and novel. Sex as a biological variable modulates the response of the BAL-derived airway organoid to hyperoxia exposure and treatment with dexamethasone. We also validated our findings in an independent dataset from human BPD lung samples. BAL-derived human lung organoids represent a cutting-edge model that bridges a critical gap in BPD research. They combine the advantages of being patient-specific and capturing developmental lung biology, with the experimental flexibility of an in vitro system.
2026-07-31 | GSE304210 | GEO
Project description:Introduction: Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in alveolar macrophages—a key immuno-inflammatory cell in the lung—can shed light on the pathogenesis of this complex disease. Methods: We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from bronchoalveolar (BAL) cells and hybridized to an Affymetrix GeneChip Human Genome U133A 2.0 microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these groups, we applied gene set enrichment analysis (GSEA) to the transcriptional profiles of BAL cells. We used false discovery rate (FDR) < 0.01 to designate significant enrichment. Results: Sarcoid patients were either non-smokers or ex-smokers, all had lung involvement and only 2 were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression between sarcoidosis and healthy subjects revealed over 1200 differentially expressed genes at an FDR cutoff < 0.01. Several previously described immune mediators, such as interferon gamma, were up-regulated in the sarcoidosis subjects. Since genes often exert their influence through functionally coherent modules, we performed GSEA based on global expression profiles of alveolar macrophages between the subject groups. We identified more than 200 gene sets enriched in patients with sarcoidosis whereas very few pathways were over-represented in the healthy controls. Many of the sarcoidosis-associated pathways mapped to inflammatory and immune-related processes including T-cell signaling, graft vs. host disease, IL-12, IL-23, and IL-17 pathways, and oxidative phosphorylation. However, we also found and confirmed significant alteration in Proteasome-related pathways. Conclusions: BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional networks involved in immuno-inflammatory and proteasomal processes. Our findings add to the growing evidence implicating airspace resident cells in the pathogenesis of sarcoidoisis and identify specific pathways whose activation may modulate disease progression.
2016-07-22 | GSE75023 | GEO
Project description:Pulmonary sarcoidosis is an inflammatory disease characterized by granuloma formation and heterogeneous clinical outcome. TNF is a proinflammatory cytokine contributing to granuloma formation and high levels of TNF have been shown to associate with progressive disease. Mononuclear phagocytes (MNPs) are potent producers of TNF and highly responsive to inflammation. In sarcoidosis, alveolar macrophages (AMs) have been well studied. However, MNPs also include monocytes/monocyte-derived cells and dendritic cells (DCs) that despite their central role in inflammation are poorly studied in sarcoidosis. We performed in-depth phenotypic, functional and transcriptomic analysis of MNPs subsets from blood and bronchoalveolar lavage (BAL) fluid from 108 sarcoidosis patients and 30 healthy controls.
2021-05-19 | GSE174659 | GEO
Project description:Lung tissue from fetal and neonatal lung samples is tough to obtain, and capturing cells from a living patient with evolving or established disease is very challenging. We hypothesized that airway organoids derived from BAL samples from intubated preterm neonates with established BPD will recapitulate the epithelial heterogeneity seen in human airways and can be used for studying injury and therapy responses in vitro. BPD patient BAL-derived airway organoids exhibited cellular heterogeneity consistent with that observed in the human airway. BAL sample-derived airway organoids from patients with established BPD contain basal cell progenitors and a spectrum of differentiated epithelial subtypes, including secretory, ciliated, PNECs, and hillock cells. Hyperoxia exposure and treatment with dexamethasone caused significant cellular transcriptional changes and highlighted biological pathways, both known and novel. Sex as a biological variable modulates the response of the BAL-derived airway organoid to hyperoxia exposure and treatment with dexamethasone. We also validated our findings in an independent dataset from human BPD lung samples. BAL-derived human lung organoids represent a cutting-edge model that bridges a critical gap in BPD research. They combine the advantages of being patient-specific and capturing developmental lung biology, with the experimental flexibility of an in vitro system.
2026-07-31 | GSE304202 | GEO
Project description:Lung tissue from fetal and neonatal lung samples is tough to obtain, and capturing cells from a living patient with evolving or established disease is very challenging. We hypothesized that airway organoids derived from BAL samples from intubated preterm neonates with established BPD will recapitulate the epithelial heterogeneity seen in human airways and can be used for studying injury and therapy responses in vitro. BPD patient BAL-derived airway organoids exhibited cellular heterogeneity consistent with that observed in the human airway. BAL sample-derived airway organoids from patients with established BPD contain basal cell progenitors and a spectrum of differentiated epithelial subtypes, including secretory, ciliated, PNECs, and hillock cells. Hyperoxia exposure and treatment with dexamethasone caused significant cellular transcriptional changes and highlighted biological pathways, both known and novel. Sex as a biological variable modulates the response of the BAL-derived airway organoid to hyperoxia exposure and treatment with dexamethasone. We also validated our findings in an independent dataset from human BPD lung samples. BAL-derived human lung organoids represent a cutting-edge model that bridges a critical gap in BPD research. They combine the advantages of being patient-specific and capturing developmental lung biology, with the experimental flexibility of an in vitro system.
2026-07-31 | GSE304206 | GEO
Project description:Lung tissue from fetal and neonatal lung samples is tough to obtain, and capturing cells from a living patient with evolving or established disease is very challenging. We hypothesized that airway organoids derived from BAL samples from intubated preterm neonates with established BPD will recapitulate the epithelial heterogeneity seen in human airways and can be used for studying injury and therapy responses in vitro. BPD patient BAL-derived airway organoids exhibited cellular heterogeneity consistent with that observed in the human airway. BAL sample-derived airway organoids from patients with established BPD contain basal cell progenitors and a spectrum of differentiated epithelial subtypes, including secretory, ciliated, PNECs, and hillock cells. Hyperoxia exposure and treatment with dexamethasone caused significant cellular transcriptional changes and highlighted biological pathways, both known and novel. Sex as a biological variable modulates the response of the BAL-derived airway organoid to hyperoxia exposure and treatment with dexamethasone. We also validated our findings in an independent dataset from human BPD lung samples. BAL-derived human lung organoids represent a cutting-edge model that bridges a critical gap in BPD research. They combine the advantages of being patient-specific and capturing developmental lung biology, with the experimental flexibility of an in vitro system.
2026-07-31 | GSE304208 | GEO
Project description:Lung tissue from fetal and neonatal lung samples is tough to obtain, and capturing cells from a living patient with evolving or established disease is very challenging. We hypothesized that airway organoids derived from BAL samples from intubated preterm neonates with established BPD will recapitulate the epithelial heterogeneity seen in human airways and can be used for studying injury and therapy responses in vitro. BPD patient BAL-derived airway organoids exhibited cellular heterogeneity consistent with that observed in the human airway. BAL sample-derived airway organoids from patients with established BPD contain basal cell progenitors and a spectrum of differentiated epithelial subtypes, including secretory, ciliated, PNECs, and hillock cells. Hyperoxia exposure and treatment with dexamethasone caused significant cellular transcriptional changes and highlighted biological pathways, both known and novel. Sex as a biological variable modulates the response of the BAL-derived airway organoid to hyperoxia exposure and treatment with dexamethasone. We also validated our findings in an independent dataset from human BPD lung samples. BAL-derived human lung organoids represent a cutting-edge model that bridges a critical gap in BPD research. They combine the advantages of being patient-specific and capturing developmental lung biology, with the experimental flexibility of an in vitro system.
2026-07-31 | GSE304203 | GEO