Induced pluripotent stem cells (iPSCs) are an essential tool for modeling how causal genetic variants impact cellular function in disease, as well as an emerging source of tissue for regenerative medicine. The preparation of somatic cells, their reprogramming and the subsequent verification of iPSC pluripotency are laborious, manual processes limiting the scale and reproducibility of this technology. Here we describe a modular, robotic platform for iPSC reprogramming enabling automated, high-throughput conversion of skin biopsies into iPSCs and differentiated cells with minimal manual intervention. We demonstrate that automated reprogramming and the pooled selection of polyclonal pluripotent cells results in high-quality, stable iPSCs. These lines display less line-to-line variation than either manually produced lines or lines produced through automation followed by single-colony subcloning. The robotic platform we describe will enable the application of iPSCs to population-scale biomedical problems including the study of complex genetic diseases and the development of personalized medicines.

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We thank L. Rubin, Z. Hall and S. Lipnick for critical reading of the manuscript. This work would not have been possible without S. Solomon's leadership, vision, continual encouragement and unstinting support. The authors also thank The Genomics Core, National Human Genome Research Institute, for performing the SNP arrays and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, Bethesda, USA for their contributions. A.M. receives support as a New York Stem Cell Foundation Robertson Investigator, with additional funding through US National Institutes of Health grant P01GM099117.

Author information

Author notes

    • Keren A Weiss
    •  & David J Kahler

    Present addresses: New York University School of Medicine, RNAi High Throughput Screening Core, New York, New York, USA (D.J.K.); Department of Cell & Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia (K.A.W.).

    • Daniel Paull
    • , Ana Sevilla
    • , Hongyan Zhou
    • , Aana Kim Hahn
    • , Hesed Kim
    •  & Christopher Napolitano

    These authors contributed equally to this work.


  1. The New York Stem Cell Foundation Research Institute, New York, New York, USA.

    • Daniel Paull
    • , Ana Sevilla
    • , Hongyan Zhou
    • , Aana Kim Hahn
    • , Hesed Kim
    • , Christopher Napolitano
    • , Linshan Shang
    • , Katie Krumholz
    • , Premlatha Jagadeesan
    • , Chris M Woodard
    • , Bruce Sun
    • , Matthew Zimmer
    • , Eliana Forero
    • , Dorota N Moroziewicz
    • , Hector Martinez
    • , Keren A Weiss
    • , Lauren B Vensand
    • , Carmen R Dusenberry
    • , Hannah Polus
    • , Karla Therese L Sy
    • , David J Kahler
    • , Susan L Solomon
    • , Stephen Chang
    •  & Scott A Noggle
  2. The Broad Institute, Cambridge, Massachusetts, USA.

    • Alexander Tsankov
    • , Alexander Meissner
    •  & Kevin Eggan
  3. The Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA.

    • Alexander Tsankov
    • , Alexander Meissner
    •  & Kevin Eggan
  4. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA.

    • Alexander Tsankov
    • , Alexander Meissner
    •  & Kevin Eggan
  5. Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.

    • Thierry Vilboux
    • , May Christine V Malicdan
    •  & William A Gahl
  6. Division of Medical Genomics, Inova Translational Medicine Institute, Inova Health System, Falls Church, Virginia, USA.

    • Thierry Vilboux
  7. NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institute of Health and National Human Genome Research Institute, National Institute of Health, Bethesda, Maryland, USA.

    • William A Gahl
  8. The Howard Hughes Medical Institute, Cambridge, Massachusetts, USA.

    • Kevin Eggan


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D.P. designed and performed iPSC reprogramming, expansion and QC assays. A.S. designed and performed iPSC expansion and RNA QC assays. H.Z. designed and performed iPSC reprogramming, selection and passaging biology. A.K.H. engineered methods for iPSC expansion and EB and fibroblast QC methods. H.K. engineered methods for fibroblast derivation, iPSC reprogramming, selection and passaging. C.N. designed the integration of the robotic platform and sample tracking systems, and contributed to engineering methods. A.T. performed statistical analysis. K.K. and P.J. performed fibroblast derivation. D.P., A.S., L.S., B.S., C.M.W., D.N.M., H.M., M.Z., K.A.W and S.A.N., performed iPSC reprogramming, expansion, QC and differentiation experiments. E.F., H.P., K.T.L.S., C.R.D. and L.B.V. were involved in the collection of fibroblast samples. T.V., M.C.V.M. and W.A.G. performed SNP genotyping and analysis. K.K., D.J.K. and S.A.N. were involved in system protocol development. S.L.S., S.C., K.E. and S.A.N. designed and supervised the project. A.M. provided statistical tools and supervised statistical analysis. D.P., K.E. and S.A.N. wrote the manuscript with contributions from other authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Daniel Paull or Scott A Noggle.

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