Reference maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines

Abstract

The developmental potential of human pluripotent stem cells suggests that they can produce disease-relevant cell types for biomedical research. However, substantial variation has been reported among pluripotent cell lines, which could affect their utility and clinical safety. Such cell-line specific differences must be better understood before one can confidently use embryonic stem (ES) or induced pluripotent stem (iPS) cells in translational research. Towards this goal we have established genome-wide reference maps of DNA methylation and gene expression for 20 previously derived human ES lines and 12 human iPS cell lines, and we have measured the in vitro differentiation propensity of these cell lines. This resource enabled us to assess the epigenetic and transcriptional similarity of ES and iPS cells and to predict the differentiation efficiency of individual cell lines. The combination of assays yields a scorecard for quick and comprehensive characterization of pluripotent cell lines.

Data & Analysis

	DNA methylation mapping	Gene expression profiling	Quantitative differentiation assay
Raw data	ZIP archive containing UCSC Genome Browser BED files with DNA methylation data for each sample: DNA methylation data	ZIP archive containing Affymetrix CEL files with gene expression data for each sample: Gene expression data	ZIP archive containing NanoString RCC files with differentiating gene expression data: Differentiation data
Normalized data	DNA methylation levels of 28,557 gene promoter regions: DNA methylation data	Gene expression levels of 15,210 Ensembl-annotated genes: Gene expression data	Differentiating gene expression levels of 500 lineage marker genes: Differentiation data
Scorecard	Deviation scorecard and reference corridor for DNA methylation: Deviation scorecard (DNA methylation)	Deviation scorecard and reference corridor for gene expression: Deviation scorecard (gene expression)	Lineage scorecard summarizing cell-line specific differentiation propensities: Lineage scorecard (differentiation)

Additional Notes

Detailed analyses of the DNA methylation data (and UCSC Genome Browser tracks for visual inspection) are available from here: DNA methylation details
The full results underlying Figure 2D of the paper are shown here: Characteristics of the most variable genes
The DNA methylation data have also been submitted to the archive of the NIH Roadmap Epigenomics Mapping Consortium and will become available online on that website
The gene expression data have also been submitted to the Gene Expression Omnibus (GEO) database
All genome coordinates on this website and in the paper are relative to the NCBI36/hg18 assembly of the human genome

Citation

Bock C, Kiskinis E, Verstappen G, Gu H, Boulting G, Smith ZD, Ziller M, Croft GF, Amoroso MW, Oakley DH, Gnirke A, Eggan K, Meissner A (2011). Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines. Cell 144, 439-452.