Single-cell phenotyping and RNA sequencing reveal novel patterns of gene expression heterogeneity and regulation during growth and stress adaptation in a unicellular eukaryote

Phenotypic cell-to-cell variability is central for microbial populations and contributes to cell function, stress adaptation and drug resistance. Gene-expression heterogeneity underpins this variability, but has been challenging to study genome-wide. Here, we report a novel approach which combines imaging of individual fission yeast cells with single-cell RNA sequencing (scRNA-seq) and Bayesian normalisation. We analyse >2000 single cells and >700 matching RNA controls in various environmental conditions that include reposnse to various stresses as well as growth and entry into stationary phase.