Genetic background drives transcriptional variation in human induced pluripotent stem cells

Human iPS cells have been generated using a diverse range of tissues from a variety of donors using different reprogramming vectors. However, these cell lines are heterogeneous, which presents a limitation for their use in disease modeling and personalized medicine. To explore the basis of this hete...

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Bibliographic Details
Published in:PLoS genetics 2014-06, Vol.10 (6), p.e1004432-e1004432
Main Authors: Rouhani, Foad, Kumasaka, Natsuhiko, de Brito, Miguel Cardoso, Bradley, Allan, Vallier, Ludovic, Gaffney, Daniel
Format: Article
Language:English
Subjects:
Adult
Base Sequence
Biology and Life Sciences
Biomedical research
Cell Differentiation - genetics
Cells, Cultured
Comparative analysis
Embryonic Stem Cells - cytology
Endothelial Cells - cytology
Epigenetic inheritance
Epigenetics
Epigenomics
Female
Fibroblasts - cytology
Gene expression
Genetic aspects
Genetic transcription
Genomes
Humans
Induced Pluripotent Stem Cells - cytology
Keratinocytes - cytology
Male
Medical research
Ontology
Principal components analysis
RNA
Sequence Alignment
Sequence Analysis, RNA
Stem cell research
Stem cells
Studies
Transcription, Genetic - genetics
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Summary:Human iPS cells have been generated using a diverse range of tissues from a variety of donors using different reprogramming vectors. However, these cell lines are heterogeneous, which presents a limitation for their use in disease modeling and personalized medicine. To explore the basis of this heterogeneity we generated 25 iPS cell lines under normalised conditions from the same set of somatic tissues across a number of donors. RNA-seq data sets from each cell line were compared to identify the majority contributors to transcriptional heterogeneity. We found that genetic differences between individual donors were the major cause of transcriptional variation between lines. In contrast, residual signatures from the somatic cell of origin, so called epigenetic memory, contributed relatively little to transcriptional variation. Thus, underlying genetic background variation is responsible for most heterogeneity between human iPS cell lines. We conclude that epigenetic effects in hIPSCs are minimal, and that hIPSCs are a stable, robust and powerful platform for large-scale studies of the function of genetic differences between individuals. Our data also suggest that future studies using hIPSCs as a model system should focus most effort on collection of large numbers of donors, rather than generating large numbers of lines from the same donor.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1004432