Disparate interferon signaling and shared aberrant basaloid cells in single-cell profiling of idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease
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PROVIDER: PRJNA657422 | ENA |
REPOSITORIES: ENA
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Project description:Idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) differ in the predominant demographics and identified genetic risk alleles of affected patients, however both diseases frequently progress to respiratory failure and death. Contrasting advanced SSc-ILD to IPF provides insight to the role dysregulated immunity may play in pulmonary fibrosis. To analyze cell-type specific transcriptome commonalities and differences between IPF and SSc-ILD, we compared single-cell RNA-sequencing (scRNA-seq) of 21 explanted lung tissue specimens from patients with advanced IPF, SSc-ILD, and organ donor controls. Comparison of IPF and SSc-ILD tissue identified divergent patterns of interferon signaling, with interferon-gamma signaling upregulated in the SPP1hi and FABP4hi macrophages, cytotoxic T cells, and natural kill cells of IPF, while type I interferon signaling and production was upregulated in the corresponding SSc-ILD populations. Plasmacytoid dendritic cells were found in diseased lungs only, and exhibited upregulated cellular stress pathways in SSc-ILD compared to IPF. Alveolar type I cells were dramatically decreased in both IPF and SSc-ILD, with a distinct transcriptome signature separating these cells by disease. KRT5-/KRT17+ aberrant basaloid cells exhibiting markers of cellular senescence and epithelial-mesenchymal transition were identified in SSc-ILD for the first time. In summary, our study utilizes the enriched capabilities of scRNA-seq to identify key divergent cell types and pathways between IPF and SSc-ILD, providing new insights into the shared and distinct mechanisms between idiopathic and autoimmune interstitial lung diseases.
2021-03-30 | GSE156310 | GEO
Project description:We report abonormally expressed genes of idiopathic interstitial pneumonia by RNA-seq analysis. BMP3 was found down-regulated in idiopathic intestital pneumonia patients, and it closely correlated with pathogenesis of disease. The role of BMP3 in advancement of idiopathic interstitial pneumonia was verified by a series of experiments. Examination of differentially expressed genes in idiopathic interstitial pneumonia. Verification the function of selected gene in pathogenesis of idiopathic interstitial pneumonia in vivo and invitro.
2015-09-19 | E-GEOD-73189 | biostudies-arrayexpress
Project description:We report abonormally expressed genes of idiopathic interstitial pneumonia by RNA-seq analysis. BMP3 was found down-regulated in idiopathic intestital pneumonia patients, and it closely correlated with pathogenesis of disease. The role of BMP3 in advancement of idiopathic interstitial pneumonia was verified by a series of experiments.
2015-09-19 | GSE73189 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) differ in the predominant demographics and identified genetic risk alleles of effected patients, however both diseases frequently progress to respiratory failure and death. Contrasting advanced SSc-ILD to IPF provides insight to the role dysregulated immunity may play in pulmonary fibrosis. To analyze cell-type specific transcriptome commonalities and differences between IPF and SSc-ILD, we compared single-cell RNA-sequencing (scRNA-seq) of 21 explanted lung tissue specimens from patients with advanced IPF, SSc-ILD, and organ donor controls. Comparison of IPF and SSc-ILD tissue identified divergent patterns of interferon signaling, with interferon-gamma signaling upregulated in the SPP1 hi and FABP4 hi macrophages, cytotoxic T cells, and natural kill cells of IPF, while type I interferon signaling and production was upregulated in the corresponding SSc-ILD populations. Plasmacytoid dendritic cells were found in diseased lungs only, and exhibited upregulated cellular stress pathways in SSc-ILD compared to IPF. Alveolar type I cells were dramatically decreased in both IPF and SSc-ILD, with a distinct transcriptome signature separating these cells by disease. KRT5-/KRT17+ aberrant basaloid cells exhibiting markers of cellular senescence and epithelial-mesenchymal transition were identified in SSc-ILD for the first time. In summary, our study utilizes the enriched capabilities of scRNA-seq to identify key divergent cell types and pathways between IPF and SSc-ILD, providing new insights into the shared and distinct mechanisms between idiopathic and autoimmune interstitial lung diseases.
| S-EPMC8042271 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) are the 2 most common forms of idiopathic interstitial pneumonia. Response to therapy and prognosis are remarkably different. The clinical-radiographic distinction between IPF and NSIP may be challenging. We sought to investigate the gene expression profile of IPF vs. NSIP We used microarray to identifiy the gene expression profiles in patients with IPF and NSIP, mixed IPF/NSIP histologic pattern and normal controls.
2018-02-06 | GSE110147 | GEO
Project description:Chronic fibrosing idiopathic interstitial pneumonia (IIP) is characterized by alveolar epithelial damage, activation of fibroblast proliferation, and loss of normal pulmonary architecture and function. This analysis was performed to investigate the genetic backgrounds of IIP and identify potential biomarkers that can aid in diagnosis and serve as novel therapeutic target.
2017-07-13 | GSE101286 | GEO
Project description:Rationale: The fibrosing idiopathic interstitial pneumonias (IIPs) are classified based on clinical, radiographic, and pathologic criteria. The separation into phenotypic subgroups is useful in predicting outcome and therapeutic strategy; however a large degree of ambiguity remains. Gene expression profiling may contribute to traditional criteria in IIPs by characterizing the dynamic biology that more accurately distinguishes subtypes of these diseases or their prognoses. Methods: We collected transcriptional and miRNA profiles on lung tissue from 167 subjects with IIP and 50 non-diseased controls. Differential expression of individual transcripts and miRNAs was identified using an ANCOVA model incorporating the clinical diagnosis of each subject as well as age, gender, and smoking status. Validation was performed in an independent cohort of 131 IIPs and 39 non-diseased controls. Results: Our results demonstrate a substantial degree of overlap in mRNA and miRNA signatures of clinical subtypes of IIP. However, we identify two subtypes of IPF/UIP based on a strong molecular signature associated with expression of cilium genes. We demonstrate that elevated expression of cilium genes is associated with more extensive microscopic honeycombing, more fibroblastic foci, higher expression of the airway mucin gene MUC5B, and better survival in an independent cohort of IPF/UIP patients. Moreover, we identify miRNAs involved in the regulation of cilium-associated gene expression that contribute to novel molecular subphenotypes of IPF. Conclusions: While subtypes of IIP are related biologically with similar transcriptional profiles, expression of cilium genes appear to identify two unique clinical presentations of IPF/UIP. 167 subjects with IIP and 50 non-diseased controls with no replicates
2013-06-21 | E-GEOD-32538 | biostudies-arrayexpress
Project description:Rationale: The fibrosing idiopathic interstitial pneumonias (IIPs) are classified based on clinical, radiographic, and pathologic criteria. The separation into phenotypic subgroups is useful in predicting outcome and therapeutic strategy; however a large degree of ambiguity remains. Gene expression profiling may contribute to traditional criteria in IIPs by characterizing the dynamic biology that more accurately distinguishes subtypes of these diseases or their prognoses. Methods: We collected transcriptional and miRNA profiles on lung tissue from 167 subjects with IIP and 50 non-diseased controls. Differential expression of individual transcripts and miRNAs was identified using an ANCOVA model incorporating the clinical diagnosis of each subject as well as age, gender, and smoking status. Validation was performed in an independent cohort of 131 IIPs and 39 non-diseased controls. Results: Our results demonstrate a substantial degree of overlap in mRNA and miRNA signatures of clinical subtypes of IIP. However, we identify two subtypes of IPF/UIP based on a strong molecular signature associated with expression of cilium genes. We demonstrate that elevated expression of cilium genes is associated with more extensive microscopic honeycombing, more fibroblastic foci, higher expression of the airway mucin gene MUC5B, and better survival in an independent cohort of IPF/UIP patients. Moreover, we identify miRNAs involved in the regulation of cilium-associated gene expression that contribute to novel molecular subphenotypes of IPF. Conclusions: While subtypes of IIP are related biologically with similar transcriptional profiles, expression of cilium genes appear to identify two unique clinical presentations of IPF/UIP. 167 subjects with IIP and 50 non-diseased controls with no replicates
2013-06-21 | E-GEOD-32537 | biostudies-arrayexpress
Project description:Gene expression profiling of idiopathic pulmonary fibrosis and non-specific interstitial pneumonia
| PRJNA432951 | ENA
Project description:Rationale: The fibrosing idiopathic interstitial pneumonias (IIPs) are classified based on clinical, radiographic, and pathologic criteria. The separation into phenotypic subgroups is useful in predicting outcome and therapeutic strategy; however a large degree of ambiguity remains. Gene expression profiling may contribute to traditional criteria in IIPs by characterizing the dynamic biology that more accurately distinguishes subtypes of these diseases or their prognoses. Methods: We collected transcriptional and miRNA profiles on lung tissue from 167 subjects with IIP and 50 non-diseased controls. Differential expression of individual transcripts and miRNAs was identified using an ANCOVA model incorporating the clinical diagnosis of each subject as well as age, gender, and smoking status. Validation was performed in an independent cohort of 131 IIPs and 39 non-diseased controls. Results: Our results demonstrate a substantial degree of overlap in mRNA and miRNA signatures of clinical subtypes of IIP. However, we identify two subtypes of IPF/UIP based on a strong molecular signature associated with expression of cilium genes. We demonstrate that elevated expression of cilium genes is associated with more extensive microscopic honeycombing, more fibroblastic foci, higher expression of the airway mucin gene MUC5B, and better survival in an independent cohort of IPF/UIP patients. Moreover, we identify miRNAs involved in the regulation of cilium-associated gene expression that contribute to novel molecular subphenotypes of IPF. Conclusions: While subtypes of IIP are related biologically with similar transcriptional profiles, expression of cilium genes appear to identify two unique clinical presentations of IPF/UIP.
2013-06-21 | GSE32538 | GEO