Allele-specific single-cell RNA sequencing reveals different architectures of intrinsic and extrinsic gene expression noises

Abstract

Gene expression noise refers to the variation of the expression level of a gene among isogenic cells in the same environment, and has two sources: extrinsic noise arising from the disparity of the cell state and intrinsic noise arising from the stochastic process of gene expression in the same cell state. Due to the low throughput of the existing method for measuring the two noise components, the architectures of intrinsic and extrinsic expression noises remain elusive. Using allele-specific single-cell RNA sequencing, we here estimate the two noise components of 3975 genes in mouse fibroblast cells. Our analyses verify predicted influences of several factors such as the TATA-box and microRNA targeting on intrinsic and extrinsic noises and reveal gene function-associated noise trends implicating the action of natural selection. These findings unravel differential regulations, optimizations, and biological consequences of intrinsic and extrinsic noises and can aid the construction of desired synthetic circuits.

scDALI: Modelling allelic heterogeneity of DNA accessibility in single-cells reveals context-specific genetic regulation

“…Integrating both approaches, by quantifying allelic imbalance in single cell data, could be a powerful strategy to dissect the functional impact of genetic variants both within and across cell types simultaneously. Prior studies have measured allele-specific properties at a single-cell level to characterize transcriptional bursting and stochasticity in gene expression 11,12 . However, single-cell studies that consider allelic regulation are only beginning to emerge 13,14 , and computational methods to model these complex relationships are not established.…”

When development is constantly but weakly perturbed - Canalization by microRNAs

“…After all, phenotypic changes are downstream of GRN variations. At the molecular level, several genes (Hallgrimsson et al 2019; Sigalova et al 2020; Sun and Zhang 2020), e.g., Hsp90 (Rutherford and Lindquist 1998), have been suggested to have the canalizing capacity.…”