Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation
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- dc.contributor.author Dhar, Riddhiman
- dc.contributor.author Missarova, Alsu, 1990-
- dc.contributor.author Lehner, Ben, 1978-
- dc.contributor.author Carey, Lucas, 1980-
- dc.date.accessioned 2019-03-05T08:13:15Z
- dc.date.available 2019-03-05T08:13:15Z
- dc.date.issued 2019
- dc.description.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 >1500 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 to 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.
- dc.description.sponsorship Work in the lab of BL was supported by a European Research Council Consolidator grant (616434), the Spanish Ministry of Economy and Competitiveness (BFU2017-89488-P and SEV-2012–0208), the AXA Research Fund, the Bettencourt Schueller Foundation, Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR SGR 1322), the EMBL Partnership, and the Generalitat/CERCA program. Work in the lab of LBC was supported by MINECO (BFU2015-68351-P) and AGAUR (2014 SGR 0974) and the Unidad de Excelencia Maria de Maeztu (MDM-2014–0370).
- dc.format.mimetype application/pdf
- dc.identifier.citation Dhar R, Missarova AM, Lehner B, Carey LB. Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation. Elife. 2019;8:e38904. DOI: 10.7554/eLife.38904
- dc.identifier.doi http://dx.doi.org/10.7554/eLife.38904
- dc.identifier.issn 2050-084X
- dc.identifier.uri http://hdl.handle.net/10230/36729
- dc.language.iso eng
- dc.publisher eLife
- dc.relation.ispartof Elife. 2019;8:e38904
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SEV2012–0208
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68351-P
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/616434
- dc.rights © Dhar et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword S. cerevisiae
- dc.subject.keyword Cell proliferation
- dc.subject.keyword Genetics
- dc.subject.keyword Genomics
- dc.subject.keyword Noise
- dc.subject.keyword Single cell
- dc.title Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion