Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation
- Center for Genomic Regulation, Spain
- Universitat Pompeu Fabra, Spain
Abstract
Mutations frequently have outcomes that differ across individuals, even when these individuals are genetically identical and share a common environment. Moreover, individual microbial and mammalian cells can vary substantially in their proliferation rates, stress tolerance, and drug resistance, with important implications for the treatment of infections and cancer. To investigate the causes of cell-to-cell variation in proliferation, we used a high-throughput automated microscopy assay to quantify the impact of deleting >1,500 genes in yeast. Mutations affecting mitochondria were particularly variable in their outcome. In both mutant and wild-type cells mitochondrial membrane potential - but not amount - varied substantially across individual cells and predicted cell-to-cell variation in proliferation, mutation outcome, stress tolerance, and resistance in a clinically used anti-fungal drug. These results suggest an important role for cell-to-cell variation in the state of an organelle in single cell phenotypic variation.
Data availability
RNA-sequencing data that support the findings of this study have been deposited in NCBI GEO with the accession code GSE104343
Article and author information
Author details
Funding
H2020 European Research Council (616434)
- Ben Lehner
AXA Research Fund
- Ben Lehner
Ministerio de Economía y Competitividad (BFU2011-26206)
- Ben Lehner
Bettencourt Schueller Foundation
- Ben Lehner
Ministerio de Economía y Competitividad (BFU2015-68351-P))
- Lucas B Carey
AGAUR
- Ben Lehner
- Lucas B Carey
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Riddhiman Dhar
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Dhar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation
eLife 8:e38904.
https://doi.org/10.7554/eLife.38904
