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

Neavin, Drew R. and Steinmann, Angela M. and Farbehi, Nona and Chiu, Han Sheng and Daniszewski, Maciej S. and Arora, Himanshi and Bermudez, Yasmin and Moutinho, Cátia and Chan, Chia-Ling and Bax, Monique and Tyebally, Mubarika and Gnanasambandapillai, Vikkitharan and Lam, Chuan E. and Nguyen, Uyen and Hernández, Damián and Lidgerwood, Grace E. and Graham, Robert M. and Hewitt, Alex W. and Pébay, Alice and Palpant, Nathan J. and Powell, Joseph E. (2023) A village in a dish model system for population-scale hiPSC studies. Nature Communications, 14 (1). ISSN 2041-1723

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Link to published document: http://doi.org/10.1038/s41467-023-38704-1

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.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 10 Jul 2023 04:10
Last Modified: 10 Jul 2023 05:05
URI: http://eprints.victorchang.edu.au/id/eprint/1415

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