Systematic genetics and single-cell imaging reveal widespread morphological pleiotropy and cell-to-cell variability.
cell-to-cell variability
endocytosis
high-content screening
phenotype classification
single-cell analysis
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
18
09
2019
revised:
16
12
2019
accepted:
15
01
2020
entrez:
18
2
2020
pubmed:
18
2
2020
medline:
4
2
2021
Statut:
ppublish
Résumé
Our ability to understand the genotype-to-phenotype relationship is hindered by the lack of detailed understanding of phenotypes at a single-cell level. To systematically assess cell-to-cell phenotypic variability, we combined automated yeast genetics, high-content screening and neural network-based image analysis of single cells, focussing on genes that influence the architecture of four subcellular compartments of the endocytic pathway as a model system. Our unbiased assessment of the morphology of these compartments-endocytic patch, actin patch, late endosome and vacuole-identified 17 distinct mutant phenotypes associated with ~1,600 genes (~30% of all yeast genes). Approximately half of these mutants exhibited multiple phenotypes, highlighting the extent of morphological pleiotropy. Quantitative analysis also revealed that incomplete penetrance was prevalent, with the majority of mutants exhibiting substantial variability in phenotype at the single-cell level. Our single-cell analysis enabled exploration of factors that contribute to incomplete penetrance and cellular heterogeneity, including replicative age, organelle inheritance and response to stress.
Identifiants
pubmed: 32064787
doi: 10.15252/msb.20199243
pmc: PMC7025093
doi:
Substances chimiques
Saccharomyces cerevisiae Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e9243Subventions
Organisme : Gouvernement du Canada|Canadian Institutes of Health Research (CIHR)
ID : FDN-143264
Pays : International
Organisme : HHS|National Institutes of Health (NIH)
ID : R01HG00583
Pays : International
Organisme : NHGRI NIH HHS
ID : R01 HG005853
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Gouvernement du Canada|Canadian Institutes of Health Research (CIHR)
ID : FDN-143265
Pays : International
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
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