Reference maps of human es and ips cell variation enable high-throughput characterization of pluripotent cell lines

Christoph Bock; Evangelos Kiskinis; Griet Verstappen; Hongcang Gu; Gabriella Boulting; Zachary D. Smith; Michael Ziller; Gist F. Croft; MacKenzie W. Amoroso; Derek H. Oakley; Andreas Gnirke; Kevin Eggan; Alexander Meissner

doi:10.1016/j.cell.2010.12.032

Reference maps of human es and ips cell variation enable high-throughput characterization of pluripotent cell lines

Christoph Bock, Evangelos Kiskinis, Griet Verstappen, Hongcang Gu, Gabriella Boulting, Zachary D. Smith, Michael Ziller, Gist F. Croft, MacKenzie W. Amoroso, Derek H. Oakley, Andreas Gnirke, Kevin Eggan^*, Alexander Meissner

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

781 Scopus citations

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. 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.

Original language	English (US)
Pages (from-to)	439-452
Number of pages	14
Journal	Cell
Volume	144
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2010.12.032
State	Published - Feb 4 2011

Funding

We are grateful to Christopher Henderson and Hynek Wichterle (Columbia University Motor Neuron Center, Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research) for sharing fibroblast and iPS cell lines prior to publication and for many helpful discussions. We would also like to thank Tarjei Mikkelsen, Eleni Tomazou, Chad Cowan, Leon Plastek, and Tim Ahfeldt for their involvement in early pilot experiments; Patrick Boyle for technical assistance; the Harvard Research Computing team for support and computation time on the Odyssey cluster; and the members of the Eggan and Meissner labs for their comments on the manuscript. Furthermore, we acknowledge the members of the Broad Institute's Genome Sequencing Platform, Genetic Analysis Platform, and Epigenomics Initiative, including Ido Amit, Fontina Kelley, Kathleen Tibbetts, Tim Fennell, Supriya Gupta, Andrew Crenshaw, Charles Epstein, and Brad Bernstein. C.B. is supported by a Feodor Lynen Fellowship from the Alexander von Humboldt Foundation. E.K. is a fellow of the European Molecular Biology Organization. K.E. is an assistant investigator of the Stowers Medical Institute, a Howard Hughes Medical Institute early career scientist, and fellow of the MacArthur Foundation. The described work was funded by the NIH Roadmap Initiative on Epigenomics (U01ES017155), the Massachusetts Life Science Center (MLSC), and the Pew Charitable Trusts. A patent has been filed for the scorecard described in the manuscript.

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2010.12.032

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title = "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. 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.",

author = "Christoph Bock and Evangelos Kiskinis and Griet Verstappen and Hongcang Gu and Gabriella Boulting and Smith, {Zachary D.} and Michael Ziller and Croft, {Gist F.} and Amoroso, {MacKenzie W.} and Oakley, {Derek H.} and Andreas Gnirke and Kevin Eggan and Alexander Meissner",

note = "Funding Information: We are grateful to Christopher Henderson and Hynek Wichterle (Columbia University Motor Neuron Center, Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research) for sharing fibroblast and iPS cell lines prior to publication and for many helpful discussions. We would also like to thank Tarjei Mikkelsen, Eleni Tomazou, Chad Cowan, Leon Plastek, and Tim Ahfeldt for their involvement in early pilot experiments; Patrick Boyle for technical assistance; the Harvard Research Computing team for support and computation time on the Odyssey cluster; and the members of the Eggan and Meissner labs for their comments on the manuscript. Furthermore, we acknowledge the members of the Broad Institute's Genome Sequencing Platform, Genetic Analysis Platform, and Epigenomics Initiative, including Ido Amit, Fontina Kelley, Kathleen Tibbetts, Tim Fennell, Supriya Gupta, Andrew Crenshaw, Charles Epstein, and Brad Bernstein. C.B. is supported by a Feodor Lynen Fellowship from the Alexander von Humboldt Foundation. E.K. is a fellow of the European Molecular Biology Organization. K.E. is an assistant investigator of the Stowers Medical Institute, a Howard Hughes Medical Institute early career scientist, and fellow of the MacArthur Foundation. The described work was funded by the NIH Roadmap Initiative on Epigenomics (U01ES017155), the Massachusetts Life Science Center (MLSC), and the Pew Charitable Trusts. A patent has been filed for the scorecard described in the manuscript. ",

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AU - Verstappen, Griet

AU - Gu, Hongcang

AU - Boulting, Gabriella

AU - Smith, Zachary D.

AU - Ziller, Michael

AU - Croft, Gist F.

AU - Amoroso, MacKenzie W.

AU - Oakley, Derek H.

AU - Gnirke, Andreas

AU - Eggan, Kevin

AU - Meissner, Alexander

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AB - 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.

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Reference maps of human es and ips cell variation enable high-throughput characterization of pluripotent cell lines

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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