Noise control: can fluctuations be tuned to impact cell-fate decisions?

Abstract

In chemistry, temperature is often used to control molecular fluctuations and push chemical reactions into a particular outcome. Similarly, biological systems might control fluctuations in gene expression to push cells to transition into alternate states. This presentation explains how gene expression fluctuations can influence cell fate transitions across diverse biological contexts. Particularly intriguing is the concept that gene expression fluctuations––also termed noise––are specifically exploited by cells. For example, small molecules can orchestrate higher-amplitude fluctuations, while maintaining mean expression levels. These enhanced fluctuations, in turn, potentiate both cellular reprogramming and differentiation. The findings that gene expression noise is harnessed by cells, raises the question of which pathways or proteins in cells might regulate noise. The presentation describes an approach that unveils the cellular pathways that control gene expression noise. In particular, we find that a protein involved in nuclear speckle (i.e., condensate) formation, regulates the noise levels of a set of mRNAs. Strikingly, this noise-regulation propagates to the protein level and impacts mESC pluripotency and differentiation. In summary, this presentation describes how fluctuations can be tuned to impact cell-fate decisions.