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Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse embryonic fibroblasts (MEFs) trisomic for chromosomes 1, 13, 16 and 19

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Charles Arthur Whittaker

PROVIDER: E-GEOD-12501 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene Expression in MEFs Trisomic for Chromosomes 1, 13, 16 and 19

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. Keywords: cell type comparison

2008-11-05 | GSE12501 | GEO

Gene expression in mouse embryonic stem cells trisomic for chromosome 6, 8, 11 and 15

Project description:Aneuploidy, an uneven number of chromosomes, leads to severe developmental defects in mammals and is also a hallmark of cancer. However, whether aneuploidy is a driving cause or a consequence of tumor formation remains controversial. Paradoxically, existing studies based on aneuploid yeast and mouse fibroblasts have shown that aneuploidy is usually detrimental to cellular fitness. Here, we examined the effects of aneuploidy on mouse embryonic stem cells. Using a novel genetic scheme, we generated a series of aneuploid cell lines that each carries an extra copy of single chromosomes and then characterized the traits shared by these cell lines. All the aneuploid cell lines had rapid proliferation rates and enhanced colony formation efficiencies. They were less dependent on growth factors for self-renewal and showed a reduced capacity to differentiate in vitro. Moreover, xenografted aneuploid stem cells formed teratomas more efficiently, with features of neoplastic progression. These findings demonstrate that aneuploidy enhances the self-renewal capacities of stem cells and reduces their differentiation abilities.

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CGH analysis of mouse embryonic stem cells trisomic for chromosome 6, 8, 11,12 and 15

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The effect of trisomic chromosomes on spatial genome organization and global transcription in embryonic stem cells

Project description:Aneuploidy frequently occurs in cancer and developmental diseases such as Down syndrome, with its functional consequences implicated in dosage effects on gene expression and global perturbation of stress response and cell proliferation pathways. However, how aneuploidy affects spatial genome organization remains less understood. In this study, we addressed this question by utilizing the previously established isogenic wild-type (WT) and trisomic mouse embryonic stem cells (mESCs). We employed a combination of Hi-C, RNA-seq, chromosome painting and nascent RNA imaging technologies to compare the spatial genome structures and gene transcription among these cells. We found that trisomy has little effect on spatial genome organization at the level of A/B compartment or topologically associating domain (TAD). Inter-chromosomal interactions are associated with chromosome regions with high gene density, active histone modifications and high transcription levels, which are confirmed by imaging. Imaging also revealed contracted chromosome volume and weakened transcriptional activity for trisomic chromosomes, suggesting potential implications for the transcriptional output of these chromosomes. Our data resources and findings may contribute to a better understanding of the consequences of aneuploidy from the angle of spatial genome organization.

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Dosage compensation can buffer copy-number variation in wild yeast

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Transcription profiling of Drosophila deficiency hemizygotes and a duplication hemizygote reveals buffering of segmental and chromosomal aneuploidies in Drosophila melanogaster

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