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

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...

Full description

Saved in:
Bibliographic Details
Published inNature communications Vol. 14; no. 1; p. 3240
Main Authors Neavin, Drew R, Steinmann, Angela M, Farbehi, Nona, Chiu, Han Sheng, Daniszewski, Maciej S, Arora, Himanshi, Bermudez, Yasmin, Moutinho, Cátia, Chan, Chia-Ling, Bax, Monique, Tyebally, Mubarika, Gnanasambandapillai, Vikkitharan, Lam, Chuan E, Nguyen, Uyen, Hernández, Damián, Lidgerwood, Grace E, Graham, Robert M, Hewitt, Alex W, Pébay, Alice, Palpant, Nathan J, Powell, Joseph E
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 09.06.2023
Nature Publishing Group UK
Nature Portfolio
Subjects
Cell culture
Cell lines
Context
Cryopreservation
Deoxyribonucleic acid
DNA
Epigenetics
Gene expression
Genomics
Health risks
Heterogeneity
Laboratories
Medical research
Phenotypes
Pluripotency
Population genetics
Population studies
Proteins
Stem cells
Towns
Villages
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-38704-1