Population-scale proteome variation in human induced pluripotent stem cells
Open accessPreprint — published as 10.7554/elife.57390
Abstract
Realising the potential of human induced pluripotent stem cell (iPSC) technology for drug discovery, disease modelling and cell therapy requires an understanding of variability across iPSC lines. While previous studies have characterized iPS cell lines genetically and transcriptionally, little is known about the variability of the iPSC proteome. Here, we present the first comprehensive proteomic iPSC dataset, analysing 202 iPSC lines derived from 151 donors. We characterise the major genetic determinants affecting proteome and transcriptome variation across iPSC lines and identify key regulatory mechanisms affecting variation in protein abundance. Our data identified >700 human iPSC protein quantitative trait loci (pQTLs). We mapped trans regulatory effects, identifying an important role for protein-protein interactions. We discovered that pQTLs show increased enrichment in disease-linked GWAS variants, compared with RNA-based eQTLs.
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References 50 · Cited by 10
- Authors
- Mirauta, B. A., Seaton, D. D., Bensaddek, D., Brenes, A., Bonder, M. J., Kilpinen, H., HipSci Consortium, Stegle, O., & Lamond, A. I.
- Affiliations
- European Bioinformatics Institute (GB)
- University of Dundee (GB)
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2018-10-11
- OpenAlex
- W2897544150
- Cited by
- 10
- References
- 50
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 1
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Apollo (cc-by)
- Funders
- Wellcome Trust (WT098503)
- Medical Research Council (WT098503)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- human induced pluripotent stem cells, protein quantitative trait loci, protein-protein interaction, transcriptome variation, GWAS variants, disease modeling
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