of transcription and translation of a bacterial protein, it is now
known that increasing transcriptional, and not translational, noise
is responsible for the variability in reporter protein expressions
[42, 44].
InSaccharomyces cerevisiae, the control of the transcription rate
of GAL contributed to the heterogeneity of reporter yEGFP pro-
tein expression within a clonal population [45]. Moreover, it was
shown that increasing the transcriptional noise propagation in the
corresponding gene regulatory network resulted in the generation
of bistable expression states of yEGFP. This pioneering work on
actual cells is a good example of how the control of noise can
non-intuitively regulate the diversity of molecular constituents in
living systems.
In a more recent study, to understand global gene expression
noise patterns of single cells during mammalian developmental
stages, transcriptome-wide RNA-Seq expressions of oocytes to
blastocysts were investigated using high-dimensional statistical
techniques (correlation metrics, Shannon entropy, and square of
coefficient of variation) [46]. Notably, gene expression variability
increased sharply from 2-cell to 4-cell stage onward in both human
and mouse (Fig.15a). In addition, a phase transition in noise
(square of coefficient of variation) patterns occurred between
2-cell and 8-cell stages (Fig.15b).
Subsequently, a stochastic transcriptional model (based on
deterministic ordinary differential equations with random pro-
cesses) was developed and fitted the model to experimental noise
patterns (Fig.15c). From the simulation results, it was concurred
that the early developmental stages were mainly dominated by low
transcriptional activity dominated by Poisson noise. The increase in
transcriptome-wide noise for the middle stage developmental cells
was due to stochastic transcriptional amplification, which generated
heterogeneity in gene expressions between individual cells. Such
heterogeneity has been shown to be necessary for cell fate diversi-
fications (seereview in ref.39). For the later stages, on top of a high
transcriptional process, the cells possess quantal activation of most
transcription factors, or are subject to more extrinsic variability such
as phenotypic diversity among individual cells. These factors
increase the general expression scatter and noise levels. Overall,
the investigations into the transcriptome-wide expressions of the
early mammalian developmental stages revealed increasing variabil-
ity and noise patterns across the mammalian development process.
This result may support the notion in chaos theory [39], where
increasing noise generated along the embryonic development pro-
cess (between 2 to 4-cell stage) may aid in generating a noisy
landscape for multi-lineage cell differentiation to proceed through
an underlying (still unknown) chaotic mechanism.198 Kumar Selvarajoo