Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation.
Antifungal Agents
/ pharmacology
DNA, Mitochondrial
/ genetics
Fluconazole
/ pharmacology
Fungal Proteins
/ genetics
Gene Deletion
Genomics
Image Processing, Computer-Assisted
Membrane Potential, Mitochondrial
Microscopy
Mitochondria
/ genetics
Mutation
Phenotype
Saccharomyces cerevisiae
/ genetics
Sequence Analysis, RNA
Single-Cell Analysis
Transcriptome
S. cerevisiae
cell proliferation
genetics
genomics
noise
single cell
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
14 01 2019
14 01 2019
Historique:
received:
04
06
2018
accepted:
13
01
2019
pubmed:
15
1
2019
medline:
19
5
2020
entrez:
15
1
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30638445
doi: 10.7554/eLife.38904
pii: 38904
pmc: PMC6366901
doi:
pii:
Substances chimiques
Antifungal Agents
0
DNA, Mitochondrial
0
Fungal Proteins
0
Fluconazole
8VZV102JFY
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Research Council
ID : 616434
Pays : International
Organisme : Ministerio de Economía y Competitividad
ID : BFU2015-68351-P)
Pays : International
Organisme : Ministerio de Economía y Competitividad
ID : BFU2011-26206
Pays : International
Organisme : H2020 European Research Council
ID : 616434
Pays : International
Informations de copyright
© 2019, Dhar et al.
Déclaration de conflit d'intérêts
RD, AM, BL, LC No competing interests declared
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