TY - JOUR
KW - Gene expression
KW - induced pluripotent stem cells
KW - RNA sequencing
KW - Stem-cell biotechnology
AU - Drew R. Neavin
AU - Angela M. Steinmann
AU - Nona Farbehi
AU - Han Sheng Chiu
AU - Maciej S. Daniszewski
AU - Himanshi Arora
AU - Yasmin Bermudez
AU - Cátia Moutinho
AU - Chia-Ling Chan
AU - Monique Bax
AU - Mubarika Tyebally
AU - Vikkitharan Gnanasambandapillai
AU - Chuan E. Lam
AU - Uyen Nguyen
AU - Damián Hernández
AU - Grace E. Lidgerwood
AU - Robert M. Graham
AU - Alex W. Hewitt
AU - Alice Pébay
AU - Nathan J. Palpant
AU - Joseph E. Powell
AB - 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.
BT - Nature Communications
DA - 2023-06-09
DO - 10.1038/s41467-023-38704-1
IS - 1
LA - en
N2 - 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.
PY - 2023
EP - 3240
T2 - Nature Communications
TI - A village in a dish model system for population-scale hiPSC studies
UR - https://www.nature.com/articles/s41467-023-38704-1
VL - 14
Y2 - 2023-06-14
SN - 2041-1723
ER -