Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

KaryoCreate: a CRISPR-based technology to study chromosome-specific aneuploidy by targeting human centromeres

ABSTRACT: Aneuploidy, the presence of chromosome gains or losses, is a hallmark of cancer and congenital syndromes. Here, we describe KaryoCreate (Karyotype CRISPR Engineered Aneuploidy Technology), a system that enables generation of chromosome-specific aneuploidies by co-expression of a sgRNA targeting chromosome-specific CENPA-binding ɑ-satellite repeats together with dCas9 fused to a mutant form of KNL1. We designed unique and highly specific sgRNAs for 19 out of 24 chromosomes. Expression of these sgRNAs with KNL1Mut-dCas9 leads to missegregation and induction of gains or losses of the targeted chromosome in cellular progeny with an average efficiency of 8% and 12% for gains and losses, respectively (up to 20%), tested and validated across 9 chromosomes. Using KaryoCreate in colon epithelial cells, we show that chromosome 18q loss, a frequent occurrence in gastrointestinal cancers, promotes resistance to TGFβ, likely due to synergistic hemizygous deletion of multiple genes. Altogether, we describe a novel technology to create and study chromosome missegregation and aneuploidy in the context of cancer and beyond.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217325 | GEO | 2023/08/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

KaryoCreate: a new CRISPR-based technology to generate chromosome-specific aneuploidy by targeting human centromeres

Project description:Aneuploidy, the presence of chromosome gains or losses, is a hallmark of cancer and congenital syndromes. Here, we describe KaryoCreate (Karyotype CRISPR Engineered Aneuploidy Technology), a system that enables generation of chromosome-specific aneuploidies by co-expression of a sgRNA targeting chromosome-specific CENPA-binding ɑ-satellite repeats together with dCas9 fused to a mutant form of KNL1. We designed unique and highly specific sgRNAs for 19 out of 24 chromosomes. Expression of these sgRNAs with KNL1Mut-dCas9 leads to missegregation and induction of gains or losses of the targeted chromosome in cellular progeny with an average efficiency of 8% and 12% for gains and losses, respectively (up to 20%), tested and validated across 9 chromosomes. Using KaryoCreate in colon epithelial cells, we show that chromosome 18q loss, a frequent occurrence in gastrointestinal cancers, promotes resistance to TGFβ, likely due to synergistic hemizygous deletion of multiple genes. Altogether, we describe a novel technology to create and study chromosome missegregation and aneuploidy in the context of cancer and beyond.

2023-08-14 | GSE215842 | GEO

Genome structure of radicicol-induced aneuploids in yeast by array CGH

Project description:Aneuploidy, a state of having uneven numbers of chromosomes, is a form of large-effect mutation able to confer adaptive phenotypes under diverse stress conditions. Here we investigate whether pleiotropic stresses could in turn induce aneuploidy in budding yeast. Radicicol was shown to induce high level missegregation of an artificial chromosome (CF). This experiment examines possible aneuploidy of other (“natural”) chromosomes induced by radicicol.

2011-12-31 | GSE34086 | GEO

Genome structure of radicicol-induced aneuploids in yeast by array CGH

2011-12-31 | E-GEOD-34086 | biostudies-arrayexpress

Bisulfite-Seq and RNA-seq profiling of Arabidopsis aneuploids

Project description:Aneuploidy refers to gains and/or losses of individual chromosomes from the normal chromosome set. The resulting gene dosage imbalance usually has a deleterious effect on the phenotype, as illustrated in humans by Down Syndrome (trisomy 21) and solid tumor cells, which are typically highly aneuploid. Aneuploidy has been studied for many years in plants and has been a factor contributing to plant chromosome evolution. Nevertheless, there is still relatively little information about how chromosome numerical imbalances affect the molecular constitution of cells and confer altered phenotypes. To investigate these questions we have performed comparative transcriptome (RNA-seq) and methylome (bisulfite-seq) analyses on trisomics (2n+1) of all five chromosomes of Arabidopsis thaliana as well as matched diploids, triploid and tetraploids.

2018-06-20 | GSE79676 | GEO

Quantitative proteomic analyses of budding yeast cells harboring an additional chromosome

Project description:Phenotypic variability is a hallmark of diseases involving chromosome gains and losses, such as Down Syndrome and cancer. Allelic variances have been thought to be the sole cause of this heterogeneity. Here, we systematically examine the consequences of gaining and losing single or multiple chromosomes to show that the aneuploid state causes non-genetic phenotypic variability. Yeast cell populations harboring the same defined aneuploidy exhibit heterogeneity in cell cycle progression and response to environmental perturbations, which we show to be partly due to gene copy number imbalances. Thus, subtle changes in gene expression severely impact the robustness of biological networks and cause alternate behaviors when they occur at a large scale. Because trisomic mice also exhibit variable phenotypes, we further propose that non-genetic individuality is a universal characteristic of the aneuploid state that could contribute to variability in presentation and treatment responses of diseases caused by aneuploidy.

2017-04-10 | PXD006009 | Pride

Protein aggregation mediates protein complex stoichiometry in aneuploid cells, part 2

Project description:Aneuploidy, a condition characterized by chromosome gains and losses, causes reduced fitness and numerous cellular stresses, including increased protein aggregation. Here, we identify protein complex stoichiometry imbalances as a major cause of protein aggregation in aneuploid cells. Subunits of protein complexes encoded on excess chromosomes aggregate in aneuploid cells, which is suppressed when expression of other subunits is coordinately altered. We further show that excess subunits are either degraded or aggregate and that protein aggregation is nearly as effective as protein degradation at lowering levels of excess proteins. Our study explains why proteotoxic stress is a universal feature of the aneuploid state and reveals protein aggregation as a form of dosage compensation to cope with disproportionate expression of protein complex subunits.

2020-05-26 | PXD011875 | Pride

Protein aggregation mediates protein complex stoichiometry in aneuploid cells, part 1

2020-05-26 | PXD011874 | Pride

Protein aggregation mediates protein complex stoichiometry in aneuploid cells, part 4

2020-05-26 | PXD011877 | Pride

Protein aggregation mediates protein complex stoichiometry in aneuploid cells, part 7

2020-05-26 | PXD011916 | Pride

Protein aggregation mediates protein complex stoichiometry in aneuploid cells, part 5

2020-05-26 | PXD011878 | Pride