Genome-wide transcriptional response to random aneuploidy in human cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE109519 | GEO | 2019/02/26
REPOSITORIES: GEO
Similar Datasets
Project description:Most cancers exhibit aneuploidy, but its functional significance in tumor development is controversial. Here, we describe ReDACT (Restoring Disomy in Aneuploid cells using CRISPR Targeting), a set of chromosome engineering tools that allow us to eliminate specific aneuploidies from cancer genomes. Using ReDACT, we created a panel of isogenic cells that have or lack common aneuploidies, and we demonstrated that trisomy of chromosome 1q is required for malignant growth in cancers harboring this alteration. Mechanistically, gaining chromosome 1q increases the expression of MDM4 and suppresses TP53 signaling, and we show that TP53 mutations are mutually-exclusive with 1q aneuploidy in human cancers. Thus, specific aneuploidies play essential roles in tumorigenesis, raising the possibility that targeting these “aneuploidy addictions” could represent a novel approach for cancer treatment.
2023-01-09 | GSE222379 | GEO
Project description:Aneuploidy, or an aberrant karyotype, results in developmental disabilities and has been implicated in tumorigenesis. However, the causes of aneuploidy-induced phenotypes and the consequences of aneuploidy on cell physiology remain poorly understood. We have performed a meta-analysis on gene expression data from aneuploid cells in diverse organisms, including yeast, plants, mice, and humans. We found highly-related gene expression patterns that are conserved between species: genes that were involved in the response to stress were consistently upregulated, while genes associated with the cell cycle and cell proliferation were downregulated in aneuploid cells. Within species, different aneuploidies induced similar changes in gene expression, independent of the specific chromosomal aberrations. Taken together, our results demonstrate that aneuploidies of different chromosomes and in different organisms impact similar cellular pathways and cause a stereotypical anti-proliferative response that must be overcome prior to transformation. These experiments are two-color hybridizations of RNA isolated from aneuploid samples vs matched wt cells, all grown to midlog phase.
2012-06-28 | E-GEOD-35853 | biostudies-arrayexpress
Project description:Aneuploidy, or an aberrant karyotype, results in developmental disabilities and has been implicated in tumorigenesis. However, the causes of aneuploidy-induced phenotypes and the consequences of aneuploidy on cell physiology remain poorly understood. We have performed a meta-analysis on gene expression data from aneuploid cells in diverse organisms, including yeast, plants, mice, and humans. We found highly-related gene expression patterns that are conserved between species: genes that were involved in the response to stress were consistently upregulated, while genes associated with the cell cycle and cell proliferation were downregulated in aneuploid cells. Within species, different aneuploidies induced similar changes in gene expression, independent of the specific chromosomal aberrations. Taken together, our results demonstrate that aneuploidies of different chromosomes and in different organisms impact similar cellular pathways and cause a stereotypical anti-proliferative response that must be overcome prior to transformation.
2012-06-29 | GSE35853 | GEO
Project description:There are many different types and origins of aneuploidy, but whether there is a uniform cellular response to aneuploidy in human cells has not been addressed so far. To uncover a uniform transcriptional response to aneuploidy we evaluted the transcription profiles of trisomic and tetrasomic cell lines and cell lines with complex aneuploid karyotypes.
2014-02-19 | GSE47830 | GEO
Project description:Aneuploidy is a frequent feature of human tumors. Germline mutations leading to aneuploidy are very rare in humans, and their tumor-promoting properties are mostly unknown at the molecular level. We report here novel germline biallelic mutations in MAD1L1, the gene encoding the Spindle Assembly Checkpoint (SAC) protein MAD1, in a 36-year-old female with a dozen of neoplasias, including five malignant tumors. Functional studies in peripheral blood cells demonstrated lack of full-length protein and deficient SAC response, resulting in ~30-40% of aneuploid cells as detected by cytogenetic and single-cell (sc) DNA analysis. scRNA-seq analysis of proband blood cells identified mitochondrial stress accompanied by systemic inflammation with enhanced interferon and NFkB signaling. The inference of chromosomal aberrations from scRNA-seq analysis detected inflammatory signals both in aneuploid and euploid cells, suggesting a non-cell autonomous response to aneuploidy. In addition to random aneuploidies, MAD1L1 mutations resulted in specific clonal expansions of T-cells with chromosome 18 gains and enhanced cytotoxic profile, as well as intermediate B-cells with chromosome 12 gains and transcriptomic signatures characteristic of chronic lymphocytic leukemia cells. These data point to MAD1L1 mutations as the cause of a new variant of mosaic variegated aneuploidy syndrome (MVA) with systemic inflammation and unprecedented tumor susceptibility.
2023-03-11 | PXD035765 | Pride
Project description:Aneuploidy, a state of karyotype imbalance, is a hallmark of cancer. Changes in chromosome copy number have been proposed to drive disease by modulating the dosage of cancer driver genes and by promoting cancer genome evolution. Given the potential of cells with abnormal karyotypes to become cancerous, do pathways exist that limit the prevalence of such cells? By investigating the immediate consequences of aneuploidy on cell physiology, we identified mechanisms that eliminate aneuploid cells. We find that chromosome mis-segregation leads to replication stress, generating further genomic instability, increased karyotype complexity, and ultimately cell cycle arrest. Cells with complex karyotypes exhibit features of senescence and a pro-inflammatory response that promotes their clearance by the immune system. We propose that cells with abnormal karyotypes generate a signal for their own elimination that might well be a source of cancer cell immunosurveillance that must be overcome during malignant transformation.
2017-06-20 | GSE83647 | GEO
Project description:Genome-wide transcriptional response to random aneuploidy in human cells
| PRJNA431296 | ENA
Project description:There are many different types and origins of aneuploidy, but whether there is a uniform cellular response to aneuploidy in human cells has not been addressed so far. To uncover a uniform transcriptional response to aneuploidy we evaluted the transcription profiles of trisomic and tetrasomic cell lines and cell lines with complex aneuploid karyotypes. mRNA expression analysis of aneuploid cell lines derived from HCT116 compared to the HCT116 diploid cell line. With the exception of HCT116 3/3, three biological replicates of the Microarray experiment were performed.
2014-02-19 | E-GEOD-47830 | biostudies-arrayexpress
Project description:Aneuploidy and the evolution of aneuploid karyotypes of Candida albicans strains was identified using aCGH. Whole chromosome and segmental aneuploidies, (specifically on the left arm of chromosome 5 - shown to be due to isochromosome formation) are associated with the appearance of resistance to the antifungal drug fluconazole. Keywords: Comparative Genomic Hybridization
2006-06-30 | GSE4995 | GEO
Project description:Aneuploidy causes a proliferative disadvantage in all normal cells analyzed to date, yet this condition is associated with a disease characterized by unabated proliferative potential, cancer. The mechanisms that allow cancer cells to tolerate the adverse effects of aneuploidy are not known. To probe this question, we identified aneuploid yeast strains with improved proliferative abilities. Their molecular characterization revealed strain-specific genetic alterations as well as mutations shared between different aneuploid strains. Among the latter, a loss-of-function mutation in the gene encoding the deubiquitinating enzyme Ubp6 improves growth rates in four different aneuploid yeast strains by attenuating the changes in intracellular protein composition caused by aneuploidy. Our results demonstrate the existence of aneuploidy-tolerating mutations that improve the fitness of multiple different aneuploidies and highlight the importance of ubiquitin-proteasomal degradation in suppressing the adverse effects of aneuploidy.
2010-02-25 | GSE20464 | GEO