You are here

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

Title: Influence of ATM-Mediated DNA Damage Response on Genomic Variation in Human Induced Pluripotent Stem Cells.
1 views
0 downloads
Name(s): Lu, Junjie, author
Li, Hu, author
Baccei, Anna, author
Sasaki, Takayo, author
Gilbert, David M, author
Lerou, Paul H, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2016-05-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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 (RV) 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 DDR reveals unique vulnerability of early replicating open chromatin to RV vectors.
Identifier: FSU_pmch_26935587 (IID), 10.1089/scd.2015.0393 (DOI), PMC4854209 (PMCID), 26935587 (RID), 26935587 (EID)
Grant Number: P01 GM085354, R01 GM083337, R21 CA161666, R00 HD061981
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854209.
Subject(s): Animals
Ataxia Telangiectasia Mutated Proteins/deficiency
Ataxia Telangiectasia Mutated Proteins/metabolism
Cells, Cultured
Cellular Reprogramming/genetics
DNA Copy Number Variations/genetics
DNA Damage/genetics
DNA Repair
DNA Replication/genetics
Genome, Human
Humans
Induced Pluripotent Stem Cells/cytology
Induced Pluripotent Stem Cells/metabolism
Mice
Stress, Physiological/genetics
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_26935587
Owner Institution: FSU
Is Part Of: Stem cells and development.
1557-8534
Issue: iss. 9, vol. 25

Choose the citation style.
Lu, J., Li, H., Baccei, A., Sasaki, T., Gilbert, D. M., & Lerou, P. H. (2016). Influence of ATM-Mediated DNA Damage Response on Genomic Variation in Human Induced Pluripotent Stem Cells. Stem Cells And Development. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_26935587