Single‐cell RNA‐seq reveals early heterogeneity during aging in yeast

The budding yeast Saccharomyces cerevisiae (S. cerevisiae) has relatively short lifespan and is genetically tractable, making it a widely used model organism in aging research. Here, we carried out a systematic and quantitative investigation of yeast aging with single‐cell resolution through transcriptomic sequencing. We optimized a single‐cell RNA sequencing (scRNA‐seq) protocol to quantitatively study the whole transcriptome profiles of single yeast cells at different ages, finding increased cell‐to‐cell transcriptional variability during aging. The single‐cell transcriptome analysis also highlighted key biological processes or cellular components, including oxidation–reduction process, oxidative stress response (OSR), translation, ribosome biogenesis and mitochondrion that underlie aging in yeast. We uncovered a molecular marker of FIT3, indicating the early heterogeneity during aging in yeast. We also analyzed the regulation of transcription factors and further characterized the distinctive temporal regulation of the OSR by YAP1 and proteasome activity by RPN4 during aging in yeast. Overall, our data profoundly reveal early heterogeneity during aging in yeast and shed light on the aging dynamics at the single cell level.