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

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, Vikkitharan Gnanasambandapillai, Chuan E. Lam, Uyen Nguyen, Damián Hernández, Grace E. Lidgerwood, Robert M. Graham, Alex W. Hewitt, Alice Pébay, Nathan J. Palpant and Joseph E. Powell ()
Additional contact information
Drew R. Neavin: Garvan Institute of Medical Research
Angela M. Steinmann: Garvan Institute of Medical Research
Nona Farbehi: Garvan Institute of Medical Research
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
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
Alex W. Hewitt: University of Melbourne
Alice Pébay: the University of Melbourne
Nathan J. Palpant: University of Queensland
Joseph E. Powell: Garvan Institute of Medical Research

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-38704-1

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