RT Journal Article
SR Electronic
T1 Genetic Variation, Not Cell Type of Origin, Underlies Regulatory Differences in iPSCs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 013888
DO 10.1101/013888
A1 Courtney L. Kagan
A1 Nicholas E Banovich
A1 Bryan J Pavlovic
A1 Kristen Patterson
A1 Irene Gallego Romero
A1 Jonathan K Pritchard
A1 Yoav Gilad
YR 2015
UL http://biorxiv.org/content/early/2015/01/19/013888.abstract
AB The advent of induced pluripotent stem cells (iPSCs)1 revolutionized Human Genetics by allowing us to generate pluripotent cells from easily accessible somatic tissues. This technology can have immense implications for regenerative medicine, but iPSCs also represent a paradigm shift in the study of complex human phenotypes, including gene regulation and disease2-5. Yet, an unresolved caveat of the iPSC model system is the extent to which reprogrammed iPSCs retain residual phenotypes from their precursor somatic cells. To directly address this issue, we used an effective study design to compare regulatory phenotypes between iPSCs derived from two types of commonly used somatic precursor cells. We show that the cell type of origin only minimally affects gene expression levels and DNA methylation in iPSCs. Instead, genetic variation is the main driver of regulatory differences between iPSCs of different donors.