Project description:The equivalency of human induced pluripotent stem cells (hiPSCs) with human embryonic stem cells (hESCs) remains controversial. Here, we devised a strategy to assess the contribution of clonal growth, reprogramming method and genetic background to transcriptional patterns in hESCs and hiPSCs. Surprisingly, transcriptional variation originating from two different genetic backgrounds was dominant over variation due to the reprogramming method or cell type of origin of pluripotent cell lines. Moreover, the few differences we detected between isogenic hESCs and hiPSCs neither predicted functional outcome, nor distinguished an independently derived, larger set of unmatched hESC/hiPSC lines. We conclude that hESCs and hiPSCs are transcriptionally and functionally highly similar and cannot be distinguished by a consistent gene expression signature. Our data further imply that genetic background variation is a major confounding factor for transcriptional comparisons of pluripotent cell lines, explaining some of the previously observed expression differences between unmatched hESCs and hiPSCs. Expression profiling of human embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and fibroblasts, mostly in triplicates.
Project description:The Human Induced Pluripotent Stem Cells Initiative (HipSci) is generating a large, high-quality reference panel of human IPSC lines. This is a submission of mass-spectrometry analyses from 6 induced pluripotent stem cell lines generated by the HipSci project.
Project description:The equivalency of human induced pluripotent stem cells (hiPSCs) with human embryonic stem cells (hESCs) remains controversial. Here, we devised a strategy to assess the contribution of clonal growth, reprogramming method and genetic background to transcriptional patterns in hESCs and hiPSCs. Surprisingly, transcriptional variation originating from two different genetic backgrounds was dominant over variation due to the reprogramming method or cell type of origin of pluripotent cell lines. Moreover, the few differences we detected between isogenic hESCs and hiPSCs neither predicted functional outcome, nor distinguished an independently derived, larger set of unmatched hESC/hiPSC lines. We conclude that hESCs and hiPSCs are transcriptionally and functionally highly similar and cannot be distinguished by a consistent gene expression signature. Our data further imply that genetic background variation is a major confounding factor for transcriptional comparisons of pluripotent cell lines, explaining some of the previously observed expression differences between unmatched hESCs and hiPSCs.
Project description:The Human Induced Pluripotent Stem Cells Initiative (HipSci) is generating a large, high-quality reference panel of human IPSC lines. This is a submission of mass-spectrometry analyses from 6 induced pluripotent stem cell lines generated by the HipSci project.
Project description:<p>Variability in induced pluripotent stem cell (iPSC) lines remains a roadblock for disease modeling and regenerative medicine. Through linear mixed models we have described different sources of gene expression variability from RNA sequencing data in 317 human iPSC lines from 101 individuals. We found that ~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 subject-specific gene expression pattern. Pathway enrichment and key driver analyses, based on predictive causal gene networks, found that Polycomb targets explain a significant part of the non-genetic variability present in iPSCs within and across individuals. These publically available iPSC lines and genetic datasets will be a resource to the scientific community and will open new avenues to reduce variability in iPSCs and improve their utility in disease modeling.</p> <p>SNP array data from individuals included in RNA-seq transcriptome profiling study of human induced pluripotent stem cells to characterize gene expression variation across individuals and within multiple iPSC lines from the same individual. Genotyping was performed on patient blood.</p> Data availability: <ul> <li>SNP-genotyping: dbGaP - current study</li> <li>RNA-seq counts: <a href="http://www.ncbi.nlm.nih.gov/geo/">GEO</a> - GSE79636</li> <li>FASTQ files: <a href="http://www.ncbi.nlm.nih.gov/sra">SRA</a> - SRP072417</li> </ul>