Intracellular Noise Level Determines Ratio Control Strategy Confined by Speed-Accuracy Trade-off

David Menn, Patrick Sochor, Hanah Goetz, Xiaojun Tian, Xiao Wang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalACS Synthetic Biology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Noise
Gene expression
Bacteria
Gene Expression
Sensory Receptor Cells
Population
Reaction Time
Blood Cells
Blood
Tuning
Cell Count
Cells
Phenotype
Networks (circuits)

Keywords

  • cell fate
  • fractional differentiation
  • ratio tuning
  • stochasticity
  • synthetic biology

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

Cite this

Intracellular Noise Level Determines Ratio Control Strategy Confined by Speed-Accuracy Trade-off. / Menn, David; Sochor, Patrick; Goetz, Hanah; Tian, Xiaojun; Wang, Xiao.

In: ACS Synthetic Biology, 01.01.2019.

Research output: Contribution to journalArticle

@article{c08831d05f9b46098d65a8c90c53a2f2,
title = "Intracellular Noise Level Determines Ratio Control Strategy Confined by Speed-Accuracy Trade-off",
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.",
keywords = "cell fate, fractional differentiation, ratio tuning, stochasticity, synthetic biology",
author = "David Menn and Patrick Sochor and Hanah Goetz and Xiaojun Tian and Xiao Wang",
year = "2019",
month = "1",
day = "1",
doi = "10.1021/acssynbio.9b00030",
language = "English (US)",
journal = "ACS Synthetic Biology",
issn = "2161-5063",
publisher = "American Chemical Society",

}

TY - JOUR

T1 - Intracellular Noise Level Determines Ratio Control Strategy Confined by Speed-Accuracy Trade-off

AU - Menn, David

AU - Sochor, Patrick

AU - Goetz, Hanah

AU - Tian, Xiaojun

AU - Wang, Xiao

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - cell fate

KW - fractional differentiation

KW - ratio tuning

KW - stochasticity

KW - synthetic biology

UR - http://www.scopus.com/inward/record.url?scp=85066623145&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066623145&partnerID=8YFLogxK

U2 - 10.1021/acssynbio.9b00030

DO - 10.1021/acssynbio.9b00030

M3 - Article

JO - ACS Synthetic Biology

JF - ACS Synthetic Biology

SN - 2161-5063

ER -