Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines

By Christoph Bock, E. Kiskinis, Griet Verstappen, H. Gu, G. Boulting, Zachary D. Smith, Michael J. Ziller, Gist F. Croft, Mackenzie W. Mathis, D. Oakley and 3 more. Cell, 2011

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SUMMARY 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. Toward 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/493cccfdeb080fddb7f2d243774ea3492c324a2c

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Citations in the corpus

Intrinsic Membrane Hyperexcitability of ALS Patient-Derived Motor Neurons (2014, methodology): “…Neuron Differentiation iPSC generation from patient fibroblasts obtained under institutional review board approval, characterization, and motor neuron differentiation were performed as described in Kiskinis et al. (2014) and Figure S5, with iPSC line scoring as done previously (Bock et al., 2011).”
Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations (2011, background): “…and the profound biological differences between individual hESCs and hiPSCs, such as the propensity to differentiate toward specific cell lineages (Bock et al., 2011; Boulting et al., 2011), this experimental system may overcome some of the shortcomings of conventional hiPSC approaches in…”
Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming (2011, background): “Acquisition of an embryonic-like metabolic state is concomitant with global transcriptional and epigenetic reorganization that includes demethylation and activation of the promoter region of pluripotency inductors (Bock et al., 2011; Plath and Lowry, 2011).”
Energy Metabolism in Human Pluripotent Stem Cells and Their Differentiated Counterparts (2011, background): “While epigenetic and transcriptomic differences have been mentioned above [9,10] other significant genetic changes in IPSCs when compared to hESCs and differentiated cells were also recently described [11,12], including higher mutation rates and copy number variation.”
Specification of tissue-resident macrophages during organogenesis (2016, methodology): “Subsequent summarization and visualization of these genes via scorecard analysis (21) (Fig.”
DNA methylome analysis using short bisulfite sequencing data (2012, background): “Although it is present at considerable levels during early development or in pluripotent cell type”
Ethical and Safety Issues of Stem Cell-Based Therapy (2018, background): “Transformation of iPSCs into tumor cells could be a consequence of oncogenic properties of the reprogramming cocktail (use of c-MYC) [33], or insertional mutagenesis induced by the reprogramming with integrating retroviral or lentiviral vectors which disrupts endogenous genes [34].”
Single-Cell DNA Methylome Sequencing and Bioinformatic Inference of Epigenomic Cell-State Dynamics (2015, background): “Essentially, composite methyl-omes redeﬁne the concept of reference epigenome corridors (Bock et al., 2011) in the context of individual samples, thus providing a new type of reference methylome map that can account for tissue heterogeneity and cell-to-cell variation.”