Abstract：
:Robust and precise ratio control of heterogeneous phenotypes within an isogenic population is an essential task, especially in the development and differentiation of a large number of cells such as bacteria, sensory receptors, and blood cells. However, the mechanisms of such ratio control are poorly understood. Here, we employ experimental and mathematical techniques to understand the combined effects of signal induction and gene expression stochasticity on phenotypic multimodality. We identify two strategies to control phenotypic ratios from an initially homogeneous population, suitable roughly to high-noise and low-noise intracellular environments, and we show that both can be used to generate precise fractional differentiation. In noisy gene expression contexts, such as those found in bacteria, induction within the circuit's bistable region is enough to cause noise-induced bimodality within a feasible time frame. However, in less noisy contexts, such as tightly controlled eukaryotic systems, spontaneous state transitions are rare and hence bimodality needs to be induced with a controlled pulse of induction that falls outside the bistable region. Finally, we show that noise levels, system response time, and ratio tuning accuracy impose trade-offs and limitations on both ratio control strategies, which guide the selection of strategy alternatives.
journal_name
ACS Synth Bioljournal_title
ACS synthetic biologyauthors
Menn D,Sochor P,Goetz H,Tian XJ,Wang Xdoi
10.1021/acssynbio.9b00030subject
Has Abstractpub_date
2019-06-21 00:00:00pages
1352-1360issue
6issn
2161-5063journal_volume
8pub_type
杂志文章abstract：:Gene expression noise arises from stochastic variation in the synthesis and degradation of mRNA and protein molecules and creates differences in protein numbers across populations of genetically identical cells. Such variability can lead to imprecision and reduced performance of both native and synthetic networks. In ...
journal_title：ACS synthetic biology
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abstract：:Antimycins are a family of natural products generated from a hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line. Although they possess an array of useful biological activities, their structural complexity makes chemical synthesis challenging, and their biosynthesis has thus far been ...
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journal_title：ACS synthetic biology
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journal_title：ACS synthetic biology
pub_type： 杂志文章,评审
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