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A village in a dish model system for population-scale hiPSC studies

Author

Listed:
  • Drew R. Neavin

    (Garvan Institute of Medical Research)

  • Angela M. Steinmann

    (Garvan Institute of Medical Research)

  • Nona Farbehi

    (Garvan Institute of Medical Research
    University of New South Wales)

  • Han Sheng Chiu

    (University of Queensland)

  • Maciej S. Daniszewski

    (the University of Melbourne)

  • Himanshi Arora

    (Garvan Institute of Medical Research)

  • Yasmin Bermudez

    (Garvan Institute of Medical Research)

  • Cátia Moutinho

    (Garvan Institute of Medical Research)

  • Chia-Ling Chan

    (Garvan Institute of Medical Research)

  • Monique Bax

    (Victor Chang Cardiac Research Institute
    UNSW Medicine & Health, UNSW Sydney)

  • Mubarika Tyebally

    (Garvan Institute of Medical Research)

  • Vikkitharan Gnanasambandapillai

    (Garvan Institute of Medical Research)

  • Chuan E. Lam

    (Garvan Institute of Medical Research)

  • Uyen Nguyen

    (Garvan Institute of Medical Research)

  • Damián Hernández

    (the University of Melbourne)

  • Grace E. Lidgerwood

    (the University of Melbourne)

  • Robert M. Graham

    (Victor Chang Cardiac Research Institute
    UNSW Medicine & Health, UNSW Sydney
    St Vincent’s Hospital)

  • Alex W. Hewitt

    (University of Melbourne
    University of Tasmania)

  • Alice Pébay

    (the University of Melbourne
    the University of Melbourne)

  • Nathan J. Palpant

    (University of Queensland)

  • Joseph E. Powell

    (Garvan Institute of Medical Research
    UNSW Cellular Genomics Futures Institute, School of Medical Sciences, University of New South Wales)

Abstract

The mechanisms by which DNA alleles contribute to disease risk, drug response, and other human phenotypes are highly context-specific, varying across cell types and different conditions. Human induced pluripotent stem cells are uniquely suited to study these context-dependent effects but cell lines from hundreds or thousands of individuals are required. Village cultures, where multiple induced pluripotent stem lines are cultured and differentiated in a single dish, provide an elegant solution for scaling induced pluripotent stem experiments to the necessary sample sizes required for population-scale studies. Here, we show the utility of village models, demonstrating how cells can be assigned to an induced pluripotent stem line using single-cell sequencing and illustrating that the genetic, epigenetic or induced pluripotent stem line-specific effects explain a large percentage of gene expression variation for many genes. We demonstrate that village methods can effectively detect induced pluripotent stem line-specific effects, including sensitive dynamics of cell states.

Suggested Citation

  • Drew R. Neavin & Angela M. Steinmann & Nona Farbehi & Han Sheng Chiu & Maciej S. Daniszewski & Himanshi Arora & Yasmin Bermudez & Cátia Moutinho & Chia-Ling Chan & Monique Bax & Mubarika Tyebally & Vi, 2023. "A village in a dish model system for population-scale hiPSC studies," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38704-1
    DOI: 10.1038/s41467-023-38704-1
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    References listed on IDEAS

    as
    1. Helena Kilpinen & Angela Goncalves & Andreas Leha & Vackar Afzal & Kaur Alasoo & Sofie Ashford & Sendu Bala & Dalila Bensaddek & Francesco Paolo Casale & Oliver J. Culley & Petr Danecek & Adam Faulcon, 2017. "Common genetic variation drives molecular heterogeneity in human iPSCs," Nature, Nature, vol. 546(7658), pages 370-375, June.
    2. Gioele La Manno & Ruslan Soldatov & Amit Zeisel & Emelie Braun & Hannah Hochgerner & Viktor Petukhov & Katja Lidschreiber & Maria E. Kastriti & Peter Lönnerberg & Alessandro Furlan & Jean Fan & Lars E, 2018. "RNA velocity of single cells," Nature, Nature, vol. 560(7719), pages 494-498, August.
    3. Helena Kilpinen & Angela Goncalves & Andreas Leha & Vackar Afzal & Kaur Alasoo & Sofie Ashford & Sendu Bala & Dalila Bensaddek & Francesco Paolo Casale & Oliver J. Culley & Petr Danecek & Adam Faulcon, 2017. "Correction: Corrigendum: Common genetic variation drives molecular heterogeneity in human iPSCs," Nature, Nature, vol. 546(7660), pages 686-686, June.
    4. M. Büttner & J. Ostner & C. L. Müller & F. J. Theis & B. Schubert, 2021. "scCODA is a Bayesian model for compositional single-cell data analysis," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
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