02290nas a2200445   4500000000100000000000100001008004100002260001500043653002000058653003500078653001900113653002800132100001900160700002400179700001700203700001900220700002600239700001900265700002000284700002000304700001900324700001600343700002200359700003600381700001700417700001600434700002300450700002400473700002100497700001900518700001700537700002200554700002100576245007200597856005500669300000900724490000700733520109000740022001401830       2023                            d  c2023-06-0910aGene expression10ainduced pluripotent stem cells10aRNA sequencing10aStem-cell biotechnology1 aDrew R. Neavin1 aAngela M. Steinmann1 aNona Farbehi1 aHan Sheng Chiu1 aMaciej S. Daniszewski1 aHimanshi Arora1 aYasmin Bermudez1 aCátia Moutinho1 aChia-Ling Chan1 aMonique Bax1 aMubarika Tyebally1 aVikkitharan Gnanasambandapillai1 aChuan E. Lam1 aUyen Nguyen1 aDamián Hernández1 aGrace E. Lidgerwood1 aRobert M. Graham1 aAlex W. Hewitt1 aAlice Pébay1 aNathan J. Palpant1 aJoseph E. Powell00aA village in a dish model system for population-scale hiPSC studies  uhttps://www.nature.com/articles/s41467-023-38704-1  a32400 v143 aThe 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.  a2041-1723