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Series GSE150686 Query DataSets for GSE150686
Status Public on May 15, 2021
Title Haploinsufficiency of ribosomal genes limits the viability of monosomic human cells by activation of the p53 pathway
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Chromosome loss that results in monosomy has detrimental consequences for human cells, but the underlying molecular mechanisms remain enigmatic. Using p53 deficient monosomic cell lines, we found that chromosome loss impairs proliferation and genomic stability. Transcriptome and proteome analysis revealed a partial compensation of the gene dosage changes that mitigates the effects of chromosome loss. Monosomy triggers global gene expression changes that differ from the effects of trisomy. Strikingly, ribosome biogenesis and translation were commonly downregulated in monosomic cells. Polysome profiling and translation analysis suggest that the defects arise due to haploinsufficiency of ribosomal genes. The ensuing ribosome biogenesis stress triggers the p53 pathway and G1 arrest when TP53 is reintroduced into monosomic cells. Accordingly, impaired ribosome biogenesis and p53 inactivation are associated with monosomy in cancer. Our first systematic study of monosomy in human cells demonstrates that haploinsufficiency of ribosomal genes presents a dominant negative phenotype of monosomy.
 
Overall design Transcriptome of human monosomic cell lines
 
Contributor(s) Storchova Z, Kumar Chunduri N, Menges P
Citation(s) 34552071
Submission date May 15, 2020
Last update date Sep 27, 2021
Contact name Gabriela Salinas
E-mail(s) Gabriela.Salinas-Riester@medizin.uni-goettingen.de
Organization name Universitaetsmedizin Goettingen
Department Department of Pathology
Lab NGS Integrative Genomics
Street address Kreuzbergring 57
City Goettingen
State/province Lower-Saxony
ZIP/Postal code 37075
Country Germany
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (33)
GSM4556416 RPE1 p53KO Rep1
GSM4556417 RPE1 p53KO Rep2
GSM4556418 RPE1 p53KO Rep3
Relations
BioProject PRJNA633154
SRA SRP261893

Download family Format
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE150686_RAW.tar 8.3 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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