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A bioinformatic assay for pluripotency in human cells

Abstract

Pluripotent stem cells (PSCs) are defined by their potential to generate all cell types of an organism. The standard assay for pluripotency of mouse PSCs is cell transmission through the germline, but for human PSCs researchers depend on indirect methods such as differentiation into teratomas in immunodeficient mice. Here we report PluriTest, a robust open-access bioinformatic assay of pluripotency in human cells based on their gene expression profiles.

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Figure 1: A multidimensional data model for assessing PSCs.
Figure 2: Output of PluriTest.

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Gene Expression Omnibus

References

  1. Daley, G.Q. et al. Cell Stem Cell 4, 200–201 (2009).

    Article  CAS  Google Scholar 

  2. Takahashi, K. & Yamanaka, S. Cell 126, 663–676 (2006).

    Article  CAS  Google Scholar 

  3. Müller, F.J. et al. Cell Stem Cell 6, 412–414 (2010).

    Article  Google Scholar 

  4. Russell, W.M.S. & Burch, R.L. The Principles of Humane Experimental Technique (Methuen, London, 1959).

  5. Müller, F.J. et al. Nature 455, 401–405 (2008).

    Article  Google Scholar 

  6. Lee, D.D. & Seung, H.S. Nature 401, 788–791 (1999).

    Article  CAS  Google Scholar 

  7. Brunet, J.P. et al. Proc. Natl. Acad. Sci. USA 101, 4164–4169 (2004).

    Article  CAS  Google Scholar 

  8. Tax, D.M.J. & Muller, K.-R. IEEE Proc. Pattern Recognition 3, 1051–4651/04 (2004).

    Google Scholar 

  9. Josephson, R. et al. Stem Cells 25, 437–446 (2007).

    Article  CAS  Google Scholar 

  10. Lukk, M. et al. Nat. Biotechnol. 28, 322–324 (2010).

    Article  CAS  Google Scholar 

  11. R Development Core Team. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, 2010).

  12. Gray, J. in Data-Intensive Scientific Discovery (eds., Hey, T., Tansley, S. and Tolle, K.) XVII–XXXI (Microsoft Research, Redmond, Washington, USA, 2009).

  13. Du, P., Kibbe, W.A. & Lin, S.M. Bioinformatics 24, 1547–1548 (2008).

    Article  CAS  Google Scholar 

  14. Doulatov, S. et al. Nat. Immunol. 11, 585–593 (2010).

    Article  CAS  Google Scholar 

  15. Parris, T.Z. et al. Clin. Cancer Res. 16, 3860–3874 (2010).

    Article  CAS  Google Scholar 

  16. Gandhi, K.S. et al. Hum. Mol. Genet. 19, 2134–2143 (2010).

    Article  CAS  Google Scholar 

  17. Kunarso, G. et al. Nat. Genet. 42, 631–634 (2010).

    Article  CAS  Google Scholar 

  18. Fuentes-Duculan, J. et al. J. Invest. Dermatol. 130, 2412–2422 (2010).

    Article  CAS  Google Scholar 

  19. Chan, E.M. et al. Nat. Biotechnol. 27, 1033–1037 (2009).

    Article  CAS  Google Scholar 

  20. Gaujoux, R. & Seoighe, C. BMC Bioinformatics 11, 367 (2010).

    Article  Google Scholar 

Download references

Acknowledgements

F.-J.M. is supported by an Else-Kröner Fresenius Stiftung fellowship. J.F.L. is supported by grants from the California Institute for Regenerative Medicine (RT1-01108, TR1-01250 and CL1-00502), the US National Institutes of Health (R21 MH087925), the Bill and Melinda Gates Foundation, the Esther O'Keeffe Foundation and the Millipore Foundation. B.M.S. is supported by Bayer Technology Services GmbH and the Deutsche Forschungsgemeinschaft (GSC 111). L.C.L. is supported by a US National Institutes of Health National Institute of Child Health and Human Development K12 Career Development award. E.P.P. was supported by New York State Stem Cell Science grant N08T-060. We thank C. Lynch and H. Tran for preparing the samples and running the arrays; A. Schuppert, S. Peterson and K. Nazor for comments, criticisms and reading the manuscript for clarity; M. Sadelain (Memorial Sloan-Kettering Cancer Center) for providing samples and data; K. Haden and I. Mikoulitch (Illumina) for help with handling Illumina BeadArray data formats and letting us use the idat.reader.dll program module in PluriTest RIA; and C. Becker, D. Barker and A. Fritz for helpful discussions.

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Authors and Affiliations

Authors

Contributions

F.-J.M. conceived and designed the study. F.-J.M. and B.M.S. developed the PluriTest algorithm. F.-J.M., J.F.L., L.C.L. and J.B.A. oversaw the sample collection, microarray analysis and coordinated biological and bioinformatic experiments. R.W., D.M., B.M.S. and A.H. implemented the online bioinformatic platform. R.W., D.M., F.-J.M., B.M.S. and G.A. provided bioinformatic analyses. E.P.P., S.D., J.E.G. and N.O.S. prepared biological samples. F.-J.M., B.M.S. and J.F.L. wrote the manuscript with input from all authors.

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Correspondence to Franz-Josef Müller.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6, Supplementary Notes 1–3 (PDF 9945 kb)

Supplementary Data

PluriTest R/Bioconductor workspace (ZIP 10836 kb)

Supplementary Table 1

Samples used for PluriTest model generation and validation (XLS 3111 kb)

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Müller, FJ., Schuldt, B., Williams, R. et al. A bioinformatic assay for pluripotency in human cells. Nat Methods 8, 315–317 (2011). https://doi.org/10.1038/nmeth.1580

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