Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE39768 | GEO | 2012/09/12
SECONDARY ACCESSION(S): PRJNA171695
REPOSITORIES: GEO
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Project description:Extra chromosome copies markedly alter the physiology of eukaryotic cells, but the underlying reasons are not well understood. We created human trisomic and tetrasomic cell lines and determined the quantitative changes in their genome, transcriptome and proteome in comparison to their diploid counterparts. Aneuploid cell lines derived from HCT116 and RPE-1 cell lines were compared to their diploid counterparts; per study, 3 biological replicates have been performed.
2012-09-12 | E-GEOD-39768 | biostudies-arrayexpress
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: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:Trisomy mapping has long been a powerful means for assigning genes to chicken microchromosome 16 (GGA16). The major histocompatibility complex (MHC-Y, MHC-B) and CD1 genes were previously assigned to GGA16 by trisomy mapping. Here we combined array comparative genomic hybridization (aCGH) with trisomy mapping to investigate unassigned genomic contigs (temporarily assigned to chrUn_random) by the chicken genome sequencing projects for sequences originating from GGA16. We used the Cornell Trisomy chicken line in our study, as this line contains an extra copy of GGA16 and crosses between these individuals generate disomic, trisomic, and tetrasomic GGA16 offspring. Through the analysis of these individuals with aCGH, we compare signal intensities from unknowns to those expected based on copy number, and putatively assign or reject assignment to GGA16 accordingly. A three-condition experiment, where individuals (n=8) are classified based on their GGA16 content, with a total of 24 individuals. Each individual is either disomic (2X), trisomic (3X) or tetrasomic (4X) for GGA16. This 'loop' design also incorporates a dye swap.
2013-11-22 | E-GEOD-47690 | biostudies-arrayexpress
Project description:Aneuploidy, and especially the presence of unpaired chromosomal axes during meiosis, can cause infertility. However, it is not known if extra, unpaired autosomal chromosome segments acquire characteristic protein modifications and undergo transcriptional silencing (meiotic silencing of unpaired chromatin, or MSUC) similar to the unpaired regions of the X and Y chromosomes during spermatogenesis. We used three mouse models of Down syndrome, involving either an extra chromosome or translocation trisomy, to test requirements and consequences of meiotic protein modification and gene silencing in spermatocytes. These models reveal that copy number alone is not sufficient for up-regulation of genes in the trisomic interval, and that MSUC-promoting modifications are not sufficient for down-regulation of genes that reside in unpaired chromatin during meiosis. The position of a trisomic region relative to a centromere, the pairing status of the centromere, and the physical extent of the unpaired chromosomal region all affected assembly of meiotic protein modifications typical of MSUC. One key determinant to modification of unpaired chromatin and infertility in trisomy male mice appears to be proximity of unpaired chromatin to a centromere. Furthermore, the presence of an extra, unpaired centromere, but not translocation trisomy, causes global misregulation of transcription in spermatocytes. Thus, neither trisomy per se, nor chromatin modifications of unpaired chromosomal segments, have major effects on gene expression or meiotic success, but an intact unpaired chromosome has profoundly negative effects on meiotic gene expression.
2008-10-11 | GSE13123 | GEO
Project description:Trisomy mapping has long been a powerful means for assigning genes to chicken microchromosome 16 (GGA16). The major histocompatibility complex (MHC-Y, MHC-B) and CD1 genes were previously assigned to GGA16 by trisomy mapping. Here we combined array comparative genomic hybridization (aCGH) with trisomy mapping to investigate unassigned genomic contigs (temporarily assigned to chrUn_random) by the chicken genome sequencing projects for sequences originating from GGA16. We used the Cornell Trisomy chicken line in our study, as this line contains an extra copy of GGA16 and crosses between these individuals generate disomic, trisomic, and tetrasomic GGA16 offspring. Through the analysis of these individuals with aCGH, we compare signal intensities from unknowns to those expected based on copy number, and putatively assign or reject assignment to GGA16 accordingly.
2013-11-22 | GSE47690 | GEO
Project description:Aneuploidy, an incorrect chromosome number, is the leading cause of miscarriages and mental retardation in humans and is a hallmark of cancer. We examined the effects of aneuploidy on primary mouse cells by generating a series of cell lines that carry an extra copy of one of four mouse chromosomes. In all four trisomic lines proliferation was impaired and metabolic properties were altered. Immortalization, the acquisition of the ability to proliferate indefinitely, was also affected by the presence of an additional chromosome, with some chromosomes inhibiting immortalization while others accelerating the process. Our data indicate that aneuploidy decreases not only organismal but also cellular fitness and elicits traits that are shared between different aneuploid cells. Experiment Overall Design: The mRNAs from 9 different mouse embryo fibroblast (MEF) lines with a normal complement of chromosomes were compared to mRNAs from 1 MEF line with three copies of chromosome 1, 4 MEF lines with three copies of chrmosome 13, 3 MEF lines with three copies of chromosome 16 and 1 MEF line with three copies of chromosome 19.
2008-11-15 | E-GEOD-12501 | biostudies-arrayexpress
Project description:Aneuploidy is prevalent in cancer, conferring fitness advantage, multidrug resistance, and poor prognosis. In contrast, experimentally induced aneuploidy often results in adverse effects and impaired proliferation. This paradox underscores the necessity of cancer cells to adapt to abnormal chromosome numbers. To identify molecular mechanisms of adaptation to aneuploidy, we initiated in vitro evolution of cells with extra chromosomes added via microcell-mediated chromosome transfer. To this end, we cultured cells in a nutrient-rich medium for 50 passages or plated the cells at a low density and selectively collected the largest colonies originating from a single cell (colony selection). The anaylsis of global proteomes of the evolved cell lines was then carried out using a TMT quantification strategy. This data set also includes data from trisomic cells with and without TP53 k.o.
2025-01-14 | PXD049124 | Pride
Project description:Aneuploidy is a major source of gene dosage imbalance due to copy number alterations (CNA) and viable human trisomies are model disorders of altered gene expression. We studied gene and allele specific expression (ASE) of 9668 single-cell fibroblasts from T21 discordant twins and from mosaic T21, T18, T13 and T8. We examined 928 single cells with deep scRNAseq. Expected and observed overexpression of trisomic genes in trisomic vs. diploid bulk RNAseq was not detectable in trisomic vs. diploid single cells. Instead, for trisomic genes with low-to-average expression, their altered gene dosage was mainly due to the higher fraction of trisomic cells simultaneously expressing these genes, in agreement with a stochastic 2-state burst-like model of transcription. These results, confirmed in a further analysis of 8740 single fibroblasts, suggest that the specific transcriptional profile of each gene contributes to the phenotypic variability of trisomies. We propose an improved model to understand the effects of CNA and, more generally, of gene regulation on gene dosage imbalance.
2019-10-08 | GSE135500 | GEO
Project description:Dosage compensation was referred as an equalized X chromosome gene expression between males and females in Drosophila. And inverse dosage effects, produced by genomic imbalance, are believed to account for this modulated expression. Here we made a global expression comparison of trisomy 2L with on extra copy of chromosome 2 long arm to normal diploid with two copies of 2L with high throughput RNA-sequencing. We want to test how about the gene expression pattern changes in those comparisons, including the genes on varied chromosome 2 long arm, some other autosomal genes except chromosome 2L and X chromosome genes. Dosage compensation with an expression level similar to normal diploid and inverse dosage effects should be detected.
2013-09-10 | GSE46354 | GEO