Genomics,Multiomics

Dataset Information

3

Influence of ATM-mediated DNA damage response on genomic variation in human induced pluripotent stem cells (Affymetrix CNV)


ABSTRACT: Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors. We isolated genomic DNA from Ataxia-telangiectasia (A-T) iPSC cells derived from patient fibroblasts virus and episomal vectors, coresponding fibroblasts, normal human fibroblast derived iPSCcells, for hybridization to the Affymetrix Genome-Wide Human SNP 6.0 Array.

OTHER RELATED OMICS DATASETS IN: PRJNA313311PRJNA313309PRJNA313310

ORGANISM(S): Homo sapiens  

SUBMITTER: Junjie Lu   Paul Lerou  Hu Li 

PROVIDER: E-GEOD-78715 | ArrayExpress | 2016-03-29

SECONDARY ACCESSION(S): GSE78715PRJNA313311

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-78715.additional.1.zip Other
E-GEOD-78715.idf.txt Idf
E-GEOD-78715.processed.1.zip Processed
E-GEOD-78715.processed.2.zip Processed
E-GEOD-78715.processed.3.zip Processed
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Publications

Influence of ATM-Mediated DNA Damage Response on Genomic Variation in Human Induced Pluripotent Stem Cells.

Lu Junjie J   Li Hu H   Baccei Anna A   Sasaki Takayo T   Gilbert David M DM   Lerou Paul H PH  

Stem cells and development 20160411 9


Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-  ...[more]

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