Open AccessMammalian gene expression variability is explained by underlying cell state
Author(s) -
Foreman Robert,
Wollman Roy
Publication year - 2020
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20199146
Subject(s) - biology , gene expression , gene , phenotype , regulation of gene expression , bursting , genetics , transcriptional regulation , gene expression profiling , transcriptome , microbiology and biotechnology , neuroscience
Gene expression variability in mammalian systems plays an important role in physiological and pathophysiological conditions. This variability can come from differential regulation related to cell state (extrinsic) and allele‐specific transcriptional bursting (intrinsic). Yet, the relative contribution of these two distinct sources is unknown. Here, we exploit the qualitative difference in the patterns of covariance between these two sources to quantify their relative contributions to expression variance in mammalian cells. Using multiplexed error robust RNA fluorescent in situ hybridization ( MERFISH ), we measured the multivariate gene expression distribution of 150 genes related to Ca 2+ signaling coupled with the dynamic Ca 2+ response of live cells to ATP . We show that after controlling for cellular phenotypic states such as size, cell cycle stage, and Ca 2+ response to ATP , the remaining variability is effectively at the Poisson limit for most genes. These findings demonstrate that the majority of expression variability results from cell state differences and that the contribution of transcriptional bursting is relatively minimal.