Systematic genetics and single-cell imaging reveal widespread morphological pleiotropy and cell-to-cell variability
Mojca Mattiazzi Usaj1, Nil Sahin1,2, Helena Friesen1
1The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
Molecular Systems Biology
|February 18, 2020
Summary
Understanding genotype-to-phenotype links requires single-cell analysis. This study reveals widespread cell variability and pleiotropy in yeast endocytic pathway genes, impacting cellular heterogeneity.
Area of Science:
- Cell Biology
- Genetics
- Systems Biology
Background:
- The genotype-to-phenotype relationship is poorly understood at the single-cell level.
- Cellular heterogeneity and morphological pleiotropy are significant challenges in biological research.
Purpose of the Study:
- To systematically assess cell-to-cell phenotypic variability in yeast.
- To investigate genes affecting the endocytic pathway's subcellular compartments.
Main Methods:
- Automated yeast genetics
- High-content screening
- Neural network-based image analysis of single cells
- Focus on endocytic pathway compartments (endocytic patch, actin patch, late endosome, vacuole)
Main Results:
- Identified 17 distinct mutant phenotypes across ~1,600 genes.
- Observed morphological pleiotropy in approximately 50% of mutants.
- Found prevalent incomplete penetrance and substantial single-cell phenotype variability.
Conclusions:
- Single-cell analysis is crucial for understanding genotype-phenotype relationships.
- Cellular heterogeneity is influenced by factors like replicative age, organelle inheritance, and stress response.
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