A yeast-optimized single-cell transcriptomics platform elucidates how mycophenolic acid and guanine alter global mRNA levels

Commun Biol. 2021 Jun 30;4(1):822. doi: 10.1038/s42003-021-02320-w.

Abstract

Stochastic gene expression leads to inherent variability in expression outcomes even in isogenic single-celled organisms grown in the same environment. The Drop-Seq technology facilitates transcriptomic studies of individual mammalian cells, and it has had transformative effects on the characterization of cell identity and function based on single-cell transcript counts. However, application of this technology to organisms with different cell size and morphology characteristics has been challenging. Here we present yeastDrop-Seq, a yeast-optimized platform for quantifying the number of distinct mRNA molecules in a cell-specific manner in individual yeast cells. Using yeastDrop-Seq, we measured the transcriptomic impact of the lifespan-extending compound mycophenolic acid and its epistatic agent guanine. Each treatment condition had a distinct transcriptomic footprint on isogenic yeast cells as indicated by distinct clustering with clear separations among the different groups. The yeastDrop-Seq platform facilitates transcriptomic profiling of yeast cells for basic science and biotechnology applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cluster Analysis
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Fungal / drug effects
  • Gene Expression Regulation, Fungal / genetics*
  • Gene Ontology
  • Guanine / metabolism
  • Guanine / pharmacology
  • Mycophenolic Acid / metabolism
  • Mycophenolic Acid / pharmacology
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods*
  • Transcriptome / drug effects
  • Transcriptome / genetics*

Substances

  • RNA, Messenger
  • Guanine
  • Mycophenolic Acid