Single-Cell RNA Sequencing of PBMCs from Clinically Stable Connective Tissue Disease-associated Interstitial Lung Disease (CTD-ILD) Patients after Lung Transplantation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE324889 | GEO | 2026/03/19
REPOSITORIES: GEO
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Project description:LncRNA microarray analysis was used to identify the pattern of lncRNA and mRNA dysregulation between connective tissue disease-associated interstitial lung diseases (CTD-ILD) and connective tissue disease without associated interstitial lung disease (CTD-NILD). Differential genes were identified by bioinformatic analysis. Relative expression levels of five differentially expressed lncRNAs and one mRNA in 120 CTD patients with or without ILD were detected by quantitative reverse-transcription PCR (qRT-PCR). The differential gene expression analysis revealed 46 lncRNAs and 133 mRNAs were upregulated while 194 lncRNAs and 85 mRNAs were downregulated in the CTD-ILD group compared to the CTD-NILD group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses identified several significant biological processes and signaling pathways, including NF-kappa B signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway, B cell receptor signaling pathway. QRT-PCR confirmed that the selected target genes were differentially expressed in different groups. In particular, the ENST00000604692 expression level was significantly higher in the ILD than the NILD group. This research has demonstrated, for the first time, the specific profile of lncRNA in PBMCs of CTD-ILD patients and the potential signal pathways related to the pathogenesis of CTD-ILD, which may provide newfound insights for the diagnosis and treatment of CTD-ILD patients.
2022-01-05 | GSE192985 | GEO
Project description:Objective: MicroRNAs (miRNAs) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from SSc-ILD patients. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 SSc-ILD patients and 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and PBMCs were isolated from healthy controls and SSc-ILD patients. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DIANA-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q<0.25). DIANA-miRPath revealed 57 KEGGs pathways related to the most dysregulated miRNAs. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts showed only mild expression of miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and showed a weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNAs are dysregulated in lungs and PBMCs of SSc-ILD patients. Based on mRNA-miRNA interaction analysis and pathway tools, miRNAs may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD. Lung biopsies taken from open lung biopsy from SSc-ILD patients (n=15 samples) and from cancer free control patients (n=5) during ressection of the lung tumor.
2016-08-01 | E-GEOD-81293 | biostudies-arrayexpress
Project description:Objective: MicroRNAs (miRNAs) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from SSc-ILD patients. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 SSc-ILD patients and 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and PBMCs were isolated from healthy controls and SSc-ILD patients. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DIANA-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q<0.25). DIANA-miRPath revealed 57 KEGGs pathways related to the most dysregulated miRNAs. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts showed only mild expression of miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and showed a weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNAs are dysregulated in lungs and PBMCs of SSc-ILD patients. Based on mRNA-miRNA interaction analysis and pathway tools, miRNAs may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD. Lung biopsies taken from open lung biopsy from SSc-ILD patients (n=15 samples) and from cancer free control patients (n=5) during ressection of the lung tumor.
2016-08-01 | E-GEOD-81292 | biostudies-arrayexpress
Project description:The mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis. A comprehensively integrative approach was used to construct a global gene regulatory network based on the perturbation of key regulatory elements, transcriptional factors and miRNAs. The data also demonstrated that several subnetworks were significantly associated with key molecules involved in the diseases. We present a broad overview of the disease at a molecular level and discuss several possibly key regulatory molecular circuits that could play central roles in facilitating the progression of ILDs. Lung tissue samples from 23 patients with IPF or related disorders were obtained from the Lung Tissue Research Consortium (www.ltrcpublic.org). 11 samples came from patients who had been diagnosed with usual interstitial pneumonia/ idiopathic pulmonary fibrosis (UIP/IPF), 5 samples came from patients with non-specific interstitial pneumonia (NSIP), the remaining from patients with uncharacterized fibrosis and from patients with other ILD variants. B. Biopsies from uninvolved lung tissue from lung cancer patients (5 samples) and from one lung transplant patient were used as controls for comparison with the ILD samples.
2011-03-24 | E-GEOD-21369 | biostudies-arrayexpress
Project description:The mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis. A comprehensively integrative approach was used to construct a global gene regulatory network based on the perturbation of key regulatory elements, transcriptional factors and miRNAs. The data also demonstrated that several subnetworks were significantly associated with key molecules involved in the diseases. We present a broad overview of the disease at a molecular level and discuss several possibly key regulatory molecular circuits that could play central roles in facilitating the progression of ILDs. Lung tissue samples from thirty patients with IPF or related disorders were obtained from the Lung Tissue Research Consortium (www.ltrcpublic.org). Ten samples came from patients who had been diagnosed with usual interstitial pneumonia/ idiopathic pulmonary fibrosis (UIP/IPF), nine samples came from patients with non-specific interstitial pneumonia (NSIP), four from patients with uncharacterized fibrosis, and the remaining samples came from patients with other ILD variants. Biopsies from uninvolved lung tissue from lung cancer patients (5 samples) and from one lung transplant patient were used as controls for comparison with the ILD samples.
2011-04-19 | E-GEOD-21394 | biostudies-arrayexpress
Project description:Objective: MicroRNAs (miRNAs) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from SSc-ILD patients. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 SSc-ILD patients and 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and PBMCs were isolated from healthy controls and SSc-ILD patients. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DIANA-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q<0.25). DIANA-miRPath revealed 57 KEGGs pathways related to the most dysregulated miRNAs. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts showed only mild expression of miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and showed a weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNAs are dysregulated in lungs and PBMCs of SSc-ILD patients. Based on mRNA-miRNA interaction analysis and pathway tools, miRNAs may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD.
2016-08-01 | GSE81293 | GEO
Project description:Objective: MicroRNAs (miRNAs) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from SSc-ILD patients. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 SSc-ILD patients and 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and PBMCs were isolated from healthy controls and SSc-ILD patients. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DIANA-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q<0.25). DIANA-miRPath revealed 57 KEGGs pathways related to the most dysregulated miRNAs. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts showed only mild expression of miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and showed a weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNAs are dysregulated in lungs and PBMCs of SSc-ILD patients. Based on mRNA-miRNA interaction analysis and pathway tools, miRNAs may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD.
2016-08-01 | GSE81292 | GEO
Project description:To understand the cellular composition and transcriptional phenotype of fibrotic lung tissue we performed single-cell RNA-seq on stromal, immune, epithelial, and endothelial cell populations from human lung explants. Tissue was collected from normal control lungs, patients with idiopathic pulmonary fibrosis (IPF), and patients with systemic sclerosis associated interstitial lung disease (SSc-ILD). Using the 10X Genomics Chromium platform, we generated transcriptional profiles of approximately 200,500 cells across 4 IPF, 3 SSc-ILD and 3 normal control lungs.
2020-12-15 | GSE159354 | GEO
Project description:we analyzed immune cells in BALF and blood samples from patients with newly developed CTD-ILD using single-cell RNA sequencing. We aimed to clarify the pathogenesis of SS-ILD and investigate its characteristics in terms of the distribution and gene expression in BALF and blood immune cells in detail compared to other diseases.
| EGAS00001007539 | EGA
Project description:Survivors of COVID-19 can experience long-term lung complications (pulmonary sequelae), but the underlying mechanisms remain unclear. While most patients with major COVID-19 lung injury eventually recover essentially completely, some experience significant residual damage. To investigate the underlying differences, we analyzed, using bronchoalveolar lavage fluid (BALF), the alveolar immune cell compartments of a group of patients with post-COVID-19 interstitial lung disease (ILD) six months after acute COVID-19. Patients were categorized into two groups, based on High-Resolution Computed Tomography (HRCT) evaluation a year later: those with persistent HRCT abnormalities compatible with fibrosis (persistent post-COVID-19 ILD, n=6) and those with resolved lung lesions (resolved post-COVID-19 ILD, n=13). Additionally, 6 patients with pre-existing ILD were included in the study, after recovery from COVID-19. Bulk RNA transcriptomics analyses of BALF cells revealed pathways of neutrophil and monocyte chemotaxis to be enriched in patients with persistent HRCT abnormalities, consistent with increased monocyte-like cell recruitment in the lungs. Furthermore, increased gene expression of markers of pro-fibrotic macrophages/monocytes, such as SPP1 and pro-inflammatory cytokines, such as Il-1b, was also observed. Conversely, patients with resolved post-COVID-19 ILD displayed BALF cell gene expression signatures indicative of T-cell activation. Additionally, BALF gene expression patterns associated with pro-fibrotic macrophage activation, neutrophil chemotaxis and downregulation of T-cell activation were also observed in patients with pre-existing fibrotic ILD following COVID-19. These findings suggest that immune response imbalance leading to prolonged activation of innate immunity and subdued adaptive immune responses may be associated with persistent post-COVID-19 ILD.
2026-02-25 | GSE291409 | GEO