Cell-to-cell heterogeneity in gene expression levels

The cell reads genetic information in the genomic DNA, expresses an appropriate amount of appropriate genes in an appropriate environment (e.g. tissue or external stimuli), and produces RNAs and proteins as gene expression products. Because the products of gene expression are responsible for many cellular functions, the nature of a cell depends on the level of gene expression.

 Unicellular organisms, such as bacteria, have the same genome sequence between cells, and even under almost the same environmental conditions, there are significant differences in the amount of gene expression products between cells and they exhibit different environmental responses (phenotypic heterogeneity). Many unicellular organisms divide to produce daughter cells with roughly the same genome sequence, but if all cells have nearly the same phenotype, they cannot tolerate rapid environmental changes and may die. However, when phenotypic diversity is large, the number of surviving cells may increase in response to rapid environmental changes. Thus, intercellular diversity of gene expression levels is considered important as a survival strategy for unicellular organisms.

 Compared with unicellular organisms, multicellular organisms have a variety of cell-cell interactions between cells, and are less likely to exhibit rapid and extreme heterogeneity in gene expression. However, it is known that the process of generating irreversible phenotypic diversity, called cell differentiation, induces a transient heterogeneity in gene expression levels, which determines cell fate.

 Heterogeneity in gene expression (phenotypic heterogeneity) results from the stochasticity of cellular gene expression (Probabilistic activation of transcription factors, binding and dissociation of transcription factors, RNA transcription, RNA degradation, RNA transport, protein translation, degradation, etc.) and of chemical reactions in the microenvironment. While, the diversity of each cell is fixed by epigenetic control such as gene regulatory network and histone modification. Cell differentiation in multicellular organisms is a prominent example. It has been suggested that a phenomenon called the transcription bursting in particular contributes to the induction of intercellular diversity in gene expression.