Journal
CELL STEM CELL
Volume 20, Issue 4, Pages 518-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2016.11.005
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Funding
- NIH [U01HL107388, R01GM114434, 1RF1AG051504-01, R01AG043076, R01DK107437, R01MH097276]
- IBM faculty award
- AHA [10FTF3360005]
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Variability in induced pluripotent stem cell (iPSC) lines remains a concern for disease modeling and regenerative medicine. We have used RNA-sequencing analysis and linear mixed models to examine the sources of gene expression variability in 317 human iPSC lines from 101 individuals. We found that similar to 50% of genome-wide expression variability is explained by variation across individuals and identified a set of expression quantitative trait loci that contribute to this variation. These analyses coupled with allele-specific expression show that iPSCs retain a donor-specific gene expression pattern. Network, pathway, and key driver analyses showed that Polycomb targets contribute significantly to the non-genetic variability seen within and across individuals, highlighting this chromatin regulator as a likely source of reprogramming-based variability. Our findings therefore shed light on variation between iPSC lines and illustrate the potential for our dataset and other similar large-scale analyses to identify underlying drivers relevant to iPSC applications.
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