Single nucleus RNAseq of VHL hemangioblastomas
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE214906 | GEO | 2025/10/01
REPOSITORIES: GEO
Similar Datasets
Project description:786-0 is a cell line derived from a clear cell renal carcinoma. Previous studies have shown that the 786-O cell line harbors an inactivating mutation in the von-Hippel Lindau (VHL) gene. Mutations in the VHL gene occur in the majority of sporadic clear cell renal cell. To determine how inactivation of the VHL affects cellular functions, we created a derivative of 786-0, which we call 786-VHL in which a functional allele of VHL has been introduced back into the 786-O cell line.
2010-06-10 | GSE22256 | GEO
Project description:Adoptive T cell therapies hold great promise in cancer treatment, but low overall response rates in patients with solid tumors underscore remaining challenges in realizing the potential of this cellular immunotherapy approach. Promoting CD8+ T cell adaptation to tissue residency represents an underutilized but promising strategy to improve tumor-infiltrating lymphocyte (TIL) function. Using mice lacking von Hippel Lindau (VHL) in CD8+ T cells and RNA-sequencing (RNA-seq), we identified tissue-resident memory (TRM)-like TIL in mouse models of malignancy. Additionally, we found that VHL-deficient TIL exhibited a core TRM signature despite an exhaustion-associated phenotype. These results reveal a key role for VHL/HIF axis in controlling the formation of a TRM CD8+ T cell subset in primary and secondary tumors that resists functional exhaustion and mediates strong anti-tumor responses.
2021-04-08 | GSE156342 | GEO
Project description:786-0 is a cell line derived from a clear cell renal carcinoma. Previous studies have shown that the 786-O cell line harbors an inactivating mutation in the von-Hippel Lindau (VHL) gene. Mutations in the VHL gene occur in the majority of sporadic clear cell renal cell. To determine how inactivation of the VHL affects cellular functions, we created a derivative of 786-0, which we call 786-VHL in which a functional allele of VHL has been introduced back into the 786-O cell line. The renal cell carcinoma cell line 786-0, which harbors a mutated allele of VHL, was compared to a cell line derived from 786-0, termed 786-VHL, that contains a functional allele of VHL. Genes whose expression characteristics were dependent on functional VHL were identified.
2010-06-23 | E-GEOD-22256 | biostudies-arrayexpress
Project description:VHL is a tumor suppressor gene involved in the oxygen-sensing pathway whose germline mutations predispose to distinct phenotypes. Heterozygous mutations predispose to von Hippel-Lindau disease characterized by the development of multiple tumors (including hemangioblastomas, renal cell carcinomas and pheochromocytomas)1-3. More recently, a specific VHL-R200W mutation was shown to be responsible for Chuvash Polycythemia in homozygous carriers whereas heterozygous individuals have no clinical manifestation4. We report here a family carrying, on the same allele, VHL mutations characteristics of the two types of disease (a Chuvash polycythemia-R200W mutation and a von Hippel-Lindau disease-R161Q mutation). Genotyping, modeling analysis and functional studies, including transcriptomic profile of the distinct mutants validated for the first time on direct HIF target genes, show a gradual capacity of the VHL mutants to regulate the hypoxia responsive pathway that correlate with the severity of the developed phenotype. Our study provide original results that illuminate genotype/phenotype correlations in von Hippel-Lindau disease.
2013-09-03 | E-MTAB-1269 | biostudies-arrayexpress
Project description:To establish the role of proximal tubular hypoxia in diabetic kidney disease, we use a mouse line with a specific deletion of von-Hippel-Lindau (VHL) in the proximal tubule and treat them with streptozotocin (STZ) to induce a type I diabetes mellitus. 10 weeks after induction of diabetes mellitus samples were collected.
2022-08-08 | GSE210401 | GEO
Project description:To unravel the potential cooperative roles of oxygen-regulated signaling pathways; von Hippel-Lindau (VHL) tumor suppressor protein and hypoxia-inducible factor (HIF) transcription factors, we have generated mutant mice with; Vhlh, Vhlh/Hif1α, Vhlh/Hif2α and Vhlh/Hif1α/Hif2α gene alleles floxed. Subsequently primary kidney cells were isolated, cultured and infected with Adenoviruses bearing either Cre/GFP or GFP expression only. Agilent cDNA microarrays were utilized to compare the gene expression profiles of the kidney epithelial cells from aforementioned cell cultures to gain insight about the molecules and signaling pathways that drive aberrant cellular proliferation in clear cell renal cell carcinoma (ccRCC).
2016-01-08 | GSE75745 | GEO
Project description:Inactivation of the E3 ubiquitin ligase protein von Hippel-Lindau (VHL) is critical to clear cell renal cell carcinomas (ccRCC) and VHL syndrome. VHL loss leads to stabilization of hypoxia-inducible factor α (HIFα) and other substrate proteins, which may drive various tumor-promoting pathways. This process is likely reversible, because even in the highly aggressive human VHL-deficient ccRCC cell line 786-O, restoring VHL expression almost completely abolishes orthotopic tumor formation in immuno-deficient mice. This result highlights the potential of treating ccRCC by re-expressing VHL with gene therapy. However, there is inadequate understanding of the consequence of VHL restoration at the molecular level. Here, we reinstalled VHL expression in 786-O and performed transcriptome, proteome and ubiquitome profiling to assess the molecular impact.
2021-10-18 | GSE186013 | GEO
Project description:Clear-cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma (up-to 70% of all RCC types). There is a very close causal correlation between ccRCC and inactivation of the tumor suppressor gene von Hippel-Lindau (VHL) located on chromosome 3p25‐26. Up to 80% of sporadic ccRCC carry genomic mutations or epigenetic inactivation of VHL and nearly 100% familial ccRCC (in VHL disease) contain VHL deficiency. Accumulating evidence has indicated that ccRCC arises at the site of chronic inflammation and this solid tumor contains a substantial number of infiltrated immune cells. This indicates that ccRCC may be induced by the interaction between kidney tubule cells carrying inactivated VHL gene and the inflammatory microenvironment. In this study we characterized the interaction between VHL-deficient kidney tubule cells and macrophages with relevance to ccRCC formation, and found that human macrophages induced by VHL-deficient kidney tubule cells exhibit distinct gene expression program containing the signatures of tumor-associated macrophages that can promote ccRCC progression.
2022-03-12 | GSE183976 | GEO
Project description:Von Hippel-Lindau (VHL) mutations disrupt vascular patterning and maturation via Notch
| PRJNA429643 | ENA
Project description:This study explores the impact of mutations in the exon 2 of the von Hippel-Lindau (VHL) gene, associated with erythrocytosis or von Hippel-Lindau disease. We analyzed 15 genetic variants, including missense and synonymous mutations, to assess their effects on VHL protein stability and splicing. Using in silico predictions and functional assays, we found that specific mutations reduce protein stability, induce exon skipping and can cause a shift in the splice donor site. This study highlighted new exonic splicing regulatory regions. Notably, by performing RNA-protein pull down we identified two novel RNA-binding proteins, hnRNP F and hnRNP AB, as key regulators of VHL splicing. Our findings reveal the limitations of current splicing prediction tools in recognizing exonic splicing enhancer (ESE) or silencer (ESS) sequences and suggest that mutations can differentially affect disease phenotypes by influencing both protein stability and splicing. These insights enhance our understanding of the molecular mechanisms underlying VHL-associated disorders, delimitate new regulatory regions and demonstrates the role of new RNA-binding proteins in VHL splicing regulation.
2025-09-25 | PXD056515 | Pride