@article{1146, keywords = {Gene expression, induced pluripotent stem cells, RNA sequencing, Stem-cell biotechnology}, author = {Drew R. Neavin and Angela M. Steinmann and Nona Farbehi and Han Sheng Chiu and Maciej S. Daniszewski and Himanshi Arora and Yasmin Bermudez and Cátia Moutinho and Chia-Ling Chan and Monique Bax and Mubarika Tyebally and Vikkitharan Gnanasambandapillai and Chuan E. Lam and Uyen Nguyen and Damián Hernández and Grace E. Lidgerwood and Robert M. Graham and Alex W. Hewitt and Alice Pébay and Nathan J. Palpant and Joseph E. Powell}, title = {A village in a dish model system for population-scale hiPSC studies}, 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.}, year = {2023}, journal = {Nature Communications}, volume = {14}, pages = {3240}, month = {2023-06-09}, issn = {2041-1723}, url = {https://www.nature.com/articles/s41467-023-38704-1}, doi = {10.1038/s41467-023-38704-1}, language = {en}, }