A single-cell resolved genotype-phenotype map using genome-wide genetic and environmental perturbations.

ABSTRACT: Heterogeneity is inherent to living organisms and it determines cell fate and phenotypic variability. Despite its ubiquity, the underlying molecular mechanisms and the genetic basis linking genotype to-phenotype heterogeneity remain a central challenge. Here we construct a yeast knockout library with a clone and genotype RNA barcoding structure suitable for genome-scale analyses to generate a high-resolution single-cell yeast transcriptome atlas of 3500 mutants under control and stress conditions. We find that transcriptional heterogeneity reflects the coordinated expression of specific gene programs, generating a continuous of cell states that can be responsive to external insults. Cell state plasticity can be genetically modulated with mutants that act as state attractors and disruption

SUBMITTER: Nadal-Ribelles M 

PROVIDER: S-EPMC11920212 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature