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Status |
Public on Jan 20, 2017 |
Title |
Spontaneous single-copy loss of TP53 in human embryonic stem cells markedly increases cell proliferation and survival [BeadChip] |
Organism |
Homo sapiens |
Experiment type |
SNP genotyping by SNP array
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Summary |
The potential safety issues related to the acquisition of common genomic aberrations in hPSC cultures are well-recognized, but these risks have not been evaluated for sporadic mutations. Here, we explore whether a sporadic mutation that spontaneously arose in a hESC culture consisting of a single-copy deletion of chr17p13.1 would confer a survival advantage to the mutant cells. Compared to wild-type cells with two normal copies of the chr17p13.1 region, the mutant cells displayed a selective advantage when exposed to stressful conditions, and retained a higher percentage of pluripotent cells after two weeks of in vitro differentiation. Knockdown of TP53, which is a gene encompassed by the deleted region, in wild-type cells mimicked the chr17p13.1 deletion phenotype. RNA sequencing analysis showed differential expression of genes in pathways related to proliferation and differentiation. Thus, phenotypic implications of sporadic mutations must be taken into consideration before using the hPSC for clinical applications.
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Overall design |
4 samples, two mutant WA09 lines with a single-copy deletion of chr17p13.1, and two wild-type WA09 lines were genotyped using the Illumina Omni5, which interrogates 4.3 million SNPs across the human genome.
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Contributor(s) |
Morey RE, Amir H, Laurent LC |
Citation(s) |
27888558 |
Submission date |
Jul 13, 2015 |
Last update date |
Apr 23, 2017 |
Contact name |
Robert E Morey |
E-mail(s) |
robmoreyucsd@gmail.com, remorey@health.ucsd.edu
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Organization name |
UCSD
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Department |
Pathology
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Lab |
Parast
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Street address |
2880 Torrey Pines Scenic Dr
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City |
La Jolla |
State/province |
CA |
ZIP/Postal code |
92037 |
Country |
USA |
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Platforms (1) |
GPL14157 |
Illumina HumanOmni5-Quad BeadChip (HumanOmni5-4v1_B) |
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Samples (4)
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This SubSeries is part of SuperSeries: |
GSE70875 |
Spontaneous single-copy loss of TP53 in human embryonic stem cells markedly increases cell proliferation and survival |
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Relations |
BioProject |
PRJNA289653 |