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PROVIDER: PRJEB96743 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Multiple Lesion-Specific Somatic Mutations and Bi-Allelic Loss of ACVRL1 in a single patient with Hereditary Haemorrhagic Telangiectasia
2025-08-31 | PRJEB96743 | EVA
Project description:Multiple Lesion-Specific Somatic Mutations and Bi-Allelic Loss of ACVRL1 in a single patient with Hereditary Haemorrhagic Telangiectasia
| PRJEB90246 | ENA
Project description:Multiple Lesion-Specific Somatic Mutations and Bi-Allelic Loss of ACVRL1 in a single patient with Hereditary Haemorrhagic Telangiectasia
| PRJEB90210 | ENA
Project description:Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominantly inherited vascular disease characterized by the presence of mucocutaneous telangiectasia and arteriovenous malformations in visceral organs. HHT is predominantly caused by mutations in ENG and ACVRL1, Which both belong to the TGF-M-NM-2 signalling pathway. Further knowledge on how a disturbance of the TGF-M-NM-2 signalling pathway leads to HHT manifestations is needed in order to identify potential therapeutic targets. As long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and constitute a sizable fraction of the human transcriptome, we wanted to assess whether lncRNAs play a role in the molecular pathogenesis of HHT. Here we used microarray analysis to profile lncRNAs to compare the expression of HHT telangiectasial and HHT non-telangiectasial nasal tissue from the same patient in a paired design. The microarray probes were re-annotated using the GENCODE v.16 dataset, identifying 4,810 probes mapping to 2,811 lncRNAs. By comparing HHT telangiectasial tissue versus HHT non-telangiectasial tissue, we identified 42 lncRNAs that are differentially expressed (q<0.001). Using GREAT, a tool that assumes cis-regulation, we showed that differently expressed lncRNAs are enriched for genomic loci involved in key pathways concerning HHT. Our study identified lncRNAs that are aberrantly expressed in HHT telangiectasia and indicates that lncRNAs may contribute to regulate protein-coding loci in HHT. Which suggest that the lncRNA component of the transcriptome deserves more attention in HHT. A deeper understanding of lncRNAs and their role in telangiectasia formation possesses potential for discovering therapeutic targets in HHT. Gene expression profiling of 80 paired nasal samples from patients with hereditary Haemorrhagic Telangiectasia (HHT), representing telangiectasial and non-telangiectasial (normal) tissue respectively. The patients were divided into HHT1 or HHT2 in regard to the germline mutation in ENG (HHT1) or ACVRL1 (HHT2). Additional controls were healthy siblings (not carrying the germline mutation) and external controls. The study was conducted using Agilent-028004 SurePrint G3 Human GE 8x60K Microarray platform.
2014-12-19 | E-GEOD-53515 | biostudies-arrayexpress
Project description:Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominantly inherited vascular disease characterized by the presence of mucocutaneous telangiectasia and arteriovenous malformations in visceral organs. HHT is predominantly caused by mutations in ENG and ACVRL1, Which both belong to the TGF-β signalling pathway. Further knowledge on how a disturbance of the TGF-β signalling pathway leads to HHT manifestations is needed in order to identify potential therapeutic targets. As long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and constitute a sizable fraction of the human transcriptome, we wanted to assess whether lncRNAs play a role in the molecular pathogenesis of HHT. Here we used microarray analysis to profile lncRNAs to compare the expression of HHT telangiectasial and HHT non-telangiectasial nasal tissue from the same patient in a paired design. The microarray probes were re-annotated using the GENCODE v.16 dataset, identifying 4,810 probes mapping to 2,811 lncRNAs. By comparing HHT telangiectasial tissue versus HHT non-telangiectasial tissue, we identified 42 lncRNAs that are differentially expressed (q<0.001). Using GREAT, a tool that assumes cis-regulation, we showed that differently expressed lncRNAs are enriched for genomic loci involved in key pathways concerning HHT. Our study identified lncRNAs that are aberrantly expressed in HHT telangiectasia and indicates that lncRNAs may contribute to regulate protein-coding loci in HHT. Which suggest that the lncRNA component of the transcriptome deserves more attention in HHT. A deeper understanding of lncRNAs and their role in telangiectasia formation possesses potential for discovering therapeutic targets in HHT.
2014-12-19 | GSE53515 | GEO
Project description:Long Non-coding RNA expression profiles in Hereditary Haemorrhagic Telangiectasia
| PRJNA232241 | ENA
Project description:Germline mutations in LKB1 predispose to hereditary Peutz-Jeghers Syndrome (PJS), manifesting with gastrointestinal polyposis. We discovered that conditional deletion of Lkb1 in stromal fibroblasts using Fsp1-Cre leads to expansion of stromal cells and gastrointestinal polyposis in mice. Here we have investigated gene expression signatures in the Fsp1-Cre;Lkb1fl/fl mouse polyps harbouring bi-allelic deletion of Lkb1 in stromal cells together with wild-type epithelium. We provide RNA-seq gene expression data of 6 polyps, 4 adjacent gastric mucosa samples and 5 wild-type gastric mucosa samples from littermate controls. Our experiment demonstrates e.g. activated cytokine signaling and inflammatory pathways in the polyps.
2018-01-05 | E-MTAB-5549 | biostudies-arrayexpress
Project description:We developed a genetically engineered conditional compound heterozygous Dicer1 mouse strain that fully recapitulates the bi-allelic mutations of DICER1 in DICER1 syndrome-associated cancers. Embryonic activation of bi-allelic Dicer1 mutations, driven by the anti-Müllerian hormone receptor 2 (Amhr2)-driven Cre strain (Amhr2+/cre), drove cancer development from oviduct. Small RNA sequencing was performed to compare the microRNA expression profiles between tumor and normal oviduct.
2023-07-18 | GSE233398 | GEO
Project description:We developed a genetically engineered conditional compound heterozygous Dicer1 mouse strain that fully recapitulates the bi-allelic mutations of DICER1 in DICER1 syndrome-associated cancers. Embryonic activation of bi-allelic Dicer1 mutations, driven by the anti-Müllerian hormone receptor 2 (Amhr2)-driven Cre strain (Amhr2+/cre), drove cancer development from oviduct. mRNA sequencing was performed to compare the mRNA expression profiles between tumor and normal oviduct.
2023-07-18 | GSE233397 | GEO
Project description:Hereditary hemorrhagic telangiectasia (HHT, alias Rendu-Osler-Weber syndrome) is an autosomal dominant genetic disease that causes vascular malformations in multiple organs. Malformations and shunts in the liver are relevant for the long-term prognosis as they can lead to heart failure. Moreover, the role of ALK-1 in the hepatic vascular niche remains elusive. In this project, we aimed to establish a novel HHT model covering hepatic involvement by the disease and to investigate the role of ALK-1 in the hepatic vascular niche. We crossed Stab2-icre mice (MGI: 6741034) with Acvrl1-floxed mice (MGI: 4398901) to generate constitutive hepatic endothelial Acvrl1 knockout (Acvrl1-HEC-KO, alias Alk1-HEC-KO) mice. To dissect microvascular transcriptomic alterations, we performed RNA sequencing of freshly isolated hepatic endothelial cells from 3 months old mice. Transcriptomic analyses revealed an arterialization of hepatic vessels accompanied by loss of LYVE-1 and induction of Endomucin. The loss of endothelial Wnt2, Wnt9b, and Rspo3 led to a disruption of hepatic metabolic zonation with a dominance of periportal genes in Alk1-HEC-KO mice and HHT patients. Furthermore, we identified PRND (alias Doppel) and placenta growth factor (PlGF) as novel candidates of HHT pathogenesis in mice. ALK-1 controls hepatic metabolic zonation via Wnt signaling and suppresses PRND and PlGF that represent novel candidates in HHT pathogenesis.
2023-04-06 | GSE184747 | GEO