Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA125719 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Acquired chromosome abnormalities in the lungs of patients with Pulmonary Arterial Hypertension (Illumina)
| PRJNA126693 | ENA
Project description:Differentially expressed proteins from the lungs of patients with pulmonary arterial hypertension (Abdul-Salam VB et al; Circulation. 2010)
2011-05-05 | PRD000291 | Pride
Project description:Vascular remodeling in pulmonary arterial hypertension (PAH) involves proliferation and migration of endothelial and smooth muscle cells, leading to obliterative vascular lesions. Previous studies have indicated that the endothelial cell proliferation is quasi-neoplastic, with evidence of monoclonality and instability of short DNA microsatellite sequences. To assess whether there is larger scale genomic instability, we performed genome-wide microarray copy number analysis on pulmonary artery endothelial (PAEC) and smooth muscle cells isolated from the lungs of PAH patients. Mosaic chromosomal abnormalities were detected in five of nine PAEC cultures from PAH lungs and zero of four controls. Fluorescent in situ hybridization analysis confirmed the presence of these abnormalities in vivo in two of three cases. One patient harbored a germline mutation of BMPR2, the primary genetic cause of PAH, and a somatic loss of chromosome-13, which constitutes a second hit in the same pathway by deleting Smad-8. In two female cases with mosaic loss of the X-chromosome, methylation analysis showed that the active X was deleted. Remarkably, one also showed completely skewed X-inactivation in the non-deleted cells, suggesting the PAEC population was clonal prior to the acquisition of the chromosome abnormality. Our data indicate a high frequency of genetically abnormal sub-clones within the lung vessels of patients with PAH and provide the first definitive evidence of a second genetic hit in a patient with a germline BMPR2 mutation. We propose that these chromosome abnormalities may confer a growth advantage and thus contribute to the progression of PAH. Cross-sectional study of genomic copy number in cells cultured from the lungs of PAH patients.
2010-05-01 | E-GEOD-21097 | biostudies-arrayexpress
Project description:Despite recent improvements in management of idiopathic pulmonary arterial hypertension, mortality remains high. Understanding the alterations in the transcriptome–phenotype of the key lung cells involved could provide insight into the drivers of pathogenesis. In this study, we examined differential gene expression of cell types implicated in idiopathic pulmonary arterial hypertension from lung explants of patients with idiopathic pulmonary arterial hypertension compared to control lungs. After tissue digestion, we analyzed all cells from three idiopathic pulmonary arterial hypertension and six control lungs using droplet-based single cell RNA-sequencing. After dimensional reduction by t-stochastic neighbor embedding, we compared the transcriptomes of endothelial cells, pericyte/smooth muscle cells, fibroblasts, and macrophage clusters, examining differential gene expression and pathways implicated by analysis of Gene Ontology Enrichment. We found that endothelial cells and pericyte/smooth muscle cells had the most differentially expressed gene profile compared to other cell types. Top differentially upregulated genes in endothelial cells included novel genes: ROBO4, APCDD1, NDST1, MMRN2, NOTCH4, and DOCK6, as well as previously reported genes: ENG, ORAI2, TFDP1, KDR, AMOTL2, PDGFB, FGFR1, EDN1, and NOTCH1. Several transcription factors were also found to be upregulated in idiopathic pulmonary arterial hypertension endothelial cells including SOX18, STRA13, LYL1, and ELK, which have known roles in regulating endothelial cell phenotype. In particular, SOX18 was implicated through bioinformatics analyses in regulating the idiopathic pulmonary arterial hypertension endothelial cell transcriptome. Furthermore, idiopathic pulmonary arterial hypertension endothelial cells upregulated expression of FAM60A and HDAC7, potentially affecting epigenetic changes in idiopathic pulmonary arterial hypertension endothelial cells. Pericyte/smooth muscle cells expressed genes implicated in regulation of cellular apoptosis and extracellular matrix organization, and several ligands for genes showing increased expression in endothelial cells. In conclusion, our study represents the first detailed look at the transcriptomic landscape across idiopathic pulmonary arterial hypertension lung cells and provides robust insight into alterations that occur in vivo in idiopathic pulmonary arterial hypertension lungs.
2021-03-24 | GSE169471 | GEO
Project description:Vascular remodeling in pulmonary arterial hypertension (PAH) involves proliferation and migration of endothelial and smooth muscle cells, leading to obliterative vascular lesions. Previous studies have indicated that the endothelial cell proliferation is quasi-neoplastic, with evidence of monoclonality and instability of short DNA microsatellite sequences. To assess whether there is larger scale genomic instability, we performed genome-wide microarray copy number analysis on pulmonary artery endothelial (PAEC) and smooth muscle cells isolated from the lungs of PAH patients. Mosaic chromosomal abnormalities were detected in five of nine PAEC cultures from PAH lungs and zero of four controls. Fluorescent in situ hybridization analysis confirmed the presence of these abnormalities in vivo in two of three cases. One patient harbored a germline mutation of BMPR2, the primary genetic cause of PAH, and a somatic loss of chromosome-13, which constitutes a second hit in the same pathway by deleting Smad-8. In two female cases with mosaic loss of the X-chromosome, methylation analysis showed that the active X was deleted. Remarkably, one also showed completely skewed X-inactivation in the non-deleted cells, suggesting the PAEC population was clonal prior to the acquisition of the chromosome abnormality. Our data indicate a high frequency of genetically abnormal sub-clones within the lung vessels of patients with PAH and provide the first definitive evidence of a second genetic hit in a patient with a germline BMPR2 mutation. We propose that these chromosome abnormalities may confer a growth advantage and thus contribute to the progression of PAH. Cross-sectional study of genomic copy number in cells cultured from the lungs of PAH patients. This study used three Affy SNP chip types: 250kNSP, 250kSTY, and 6.0
2010-05-28 | E-GEOD-20206 | biostudies-arrayexpress
Project description:Vascular remodeling in pulmonary arterial hypertension (PAH) involves proliferation and migration of endothelial and smooth muscle cells, leading to obliterative vascular lesions. Previous studies have indicated that the endothelial cell proliferation is quasi-neoplastic, with evidence of monoclonality and instability of short DNA microsatellite sequences. To assess whether there is larger scale genomic instability, we performed genome-wide microarray copy number analysis on pulmonary artery endothelial (PAEC) and smooth muscle cells isolated from the lungs of PAH patients. Mosaic chromosomal abnormalities were detected in five of nine PAEC cultures from PAH lungs and zero of four controls. Fluorescent in situ hybridization analysis confirmed the presence of these abnormalities in vivo in two of three cases. One patient harbored a germline mutation of BMPR2, the primary genetic cause of PAH, and a somatic loss of chromosome-13, which constitutes a second hit in the same pathway by deleting Smad-8. In two female cases with mosaic loss of the X-chromosome, methylation analysis showed that the active X was deleted. Remarkably, one also showed completely skewed X-inactivation in the non-deleted cells, suggesting the PAEC population was clonal prior to the acquisition of the chromosome abnormality. Our data indicate a high frequency of genetically abnormal sub-clones within the lung vessels of patients with PAH and provide the first definitive evidence of a second genetic hit in a patient with a germline BMPR2 mutation. We propose that these chromosome abnormalities may confer a growth advantage and thus contribute to the progression of PAH.
2010-05-01 | GSE20206 | GEO
Project description:Vascular remodeling in pulmonary arterial hypertension (PAH) involves proliferation and migration of endothelial and smooth muscle cells, leading to obliterative vascular lesions. Previous studies have indicated that the endothelial cell proliferation is quasi-neoplastic, with evidence of monoclonality and instability of short DNA microsatellite sequences. To assess whether there is larger scale genomic instability, we performed genome-wide microarray copy number analysis on pulmonary artery endothelial (PAEC) and smooth muscle cells isolated from the lungs of PAH patients. Mosaic chromosomal abnormalities were detected in five of nine PAEC cultures from PAH lungs and zero of four controls. Fluorescent in situ hybridization analysis confirmed the presence of these abnormalities in vivo in two of three cases. One patient harbored a germline mutation of BMPR2, the primary genetic cause of PAH, and a somatic loss of chromosome-13, which constitutes a second hit in the same pathway by deleting Smad-8. In two female cases with mosaic loss of the X-chromosome, methylation analysis showed that the active X was deleted. Remarkably, one also showed completely skewed X-inactivation in the non-deleted cells, suggesting the PAEC population was clonal prior to the acquisition of the chromosome abnormality. Our data indicate a high frequency of genetically abnormal sub-clones within the lung vessels of patients with PAH and provide the first definitive evidence of a second genetic hit in a patient with a germline BMPR2 mutation. We propose that these chromosome abnormalities may confer a growth advantage and thus contribute to the progression of PAH.
2010-05-01 | GSE21097 | GEO
Project description:<p>The transcriptome of pulmonary arterial endothelial cells from healthy lungs and from lungs of patients with idiopathic pulmonary arterial hypertension have been analyzed and specific differences in disease-relevant pathways were identified. The genes identified as altered in these patients have direct effects on pulmonary arterial endothelial cell function. This finding may underlie the inability of the pulmonary vasculature to respond to and repair the damage observed in pulmonary hypertension. </p>
| phs000998 | dbGaP
Project description:Rationale: Pulmonary arterial hypertension is a common and potentially fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. The ability to identify patients at risk for developing pulmonary hypertension would be clinically beneficial. Objective: To identify genes that are differentially expressed in peripheral blood mononuclear cells in scleroderma patients with and without pulmonary hypertension which could be used as biomarkers of disease for early diagnosis and provide insight into pathogenesis of pulmonary hypertension in at-risk populations. Methods and Results: Gene expression analysis was performed on a carefully characterized Microarray Cohort of scleroderma patients with (n=10) and without (n=10) pulmonary hypertension. Differentially expressed genes were confirmed in the Microarray Cohort and validated in a separate Validation Cohort of scleroderma patients with (n=15) and without (n=19) pulmonary hypertension by RT-qPCR. We identified inflammatory and immune-related genes including interleukin-7 receptor (IL-7R) and chemokine receptor 7 (CCR7) as differentially expressed in patients with scleroderma-associated pulmonary hypertension. Flow cytometry confirmed decreased expression of IL-7R on circulating CD4+ T cells from scleroderma patients with pulmonary hypertension. Conclusions: Differences exist in the expression of inflammatory and immune-related genes in peripheral blood cells derived from patients with scleroderma-related pulmonary hypertension compared to those with normal pulmonary artery pressures. These findings may have implications as biomarkers to screen at-risk populations to facilitate early diagnosis and provide insight into inflammatory and autoimmune mechanisms of scleroderma-related pulmonary hypertension. Gene expression analysis was performed on a carefully characterized Microarray Cohort of scleroderma patients with (n=10) and without (n=10) pulmonary hypertension. Differentially expressed genes were confirmed in the Microarray Cohort by RT-qPCR.
2010-08-30 | E-GEOD-22356 | biostudies-arrayexpress