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| Status |
Public on Feb 14, 2023 |
| Title |
Village In a Dish: A Model System for Population-scale hiPSC Studies [Affymetrix] |
| Organism |
Homo sapiens |
| Experiment type |
SNP genotyping by SNP array
Genome variation profiling by SNP array
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| 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 under different conditions. Human induced pluripotent stem cells (hiPSCs) are uniquely suited to study these context-dependent effects, but to do so requires cell lines from hundreds or thousands of individuals. Village cultures, where multiple hiPSC lines are cultured and differentiated in a single dish, provide an elegant solution for scaling hiPSC 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 back to a donor line using single-cell sequencing and addressing whether line-specific signalling alters the transcriptional profiles of companion lines in a village. We generated single-cell RNA sequence data from hiPSC lines cultured independently (uni-culture) and in villages at three independent sites. Using a mixed linear model framework, we estimate that the proportion of transcriptional variation across cells is predominantly due to donor effects, with minimal evidence of variation due to culturing in a village system. We demonstrate that the genetic, epigenetic or hiPSC line-specific effects explain a large percentage of gene expression variation for many genes, not the village status. This is reiterated by replication of previously identified genetic effects. Finally, we demonstrate consistency in the landscape of cell states between uni- and village-culture systems. We demonstrate that village methods can effectively detect hiPSC line-specific effects, including sensitive dynamics of cell states.
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| Overall design |
20 total samples analyzed, no replicates
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| Contributor(s) |
Neavin DR, Steinmann AM, Farbehi N, Chiu HS, Daniszewski MS, Arora H, Bermudez Y, Moutinho C, Chan C, Bax M, Tyebally M, Gnanasambandapillai V, Lam CE, Nguyen U, Hernández D, Lidgerwood GE, Graham B, Hewitt AW, Pébay A, Palpant NJ, Powell JE |
| Citation(s) |
37296104 |
| Submission date |
Feb 09, 2023 |
| Last update date |
Jul 07, 2023 |
| Contact name |
Drew Neavin |
| E-mail(s) |
d.neavin@garvan.org.au
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| Organization name |
Garvan Institute of Medical Research
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| Department |
Cellular Science
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| Street address |
384 Victoria St
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| City |
Darlinghurst |
| State/province |
New South Wales |
| ZIP/Postal code |
2010 |
| Country |
Australia |
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| Platforms (1) |
| GPL33111 |
[Axiom_UKB_WCSG] Affymetrix (Applied Biosystems) UK Biobank Axiom Array |
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| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE225282 |
Village In a Dish: A Model System for Population-scale hiPSC Studies |
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| Relations |
| BioProject |
PRJNA934890 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE224950_RAW.tar |
447.8 Mb |
(http)(custom) |
TAR (of CEL, TBI, VCF) |
| Processed data provided as supplementary file |
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