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How does a complex organism such as a human develop from a single cell? It all starts from a single fertilized egg which gives rise to a vast array of cell types, such as nerve cells, muscle cells, and epithelial cells that characterize the adult? Throughout development and adulthood, cellular differentiation leads cells to assume their final morphology and physiology. Differentiation is the process by which unspecialized cells become specialized to carry out distinct functions.
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Operating principles of tristable circuits regulating cellular differentiation.

Dongya Jia1, Mohit Kumar Jolly, William Harrison

  • 1Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1827, United States of America. Program in Systems, Synthetic and Physical Biology, Rice University, Houston, TX 77005-1827, United States of America.

Physical Biology
|April 27, 2017
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Summary
This summary is machine-generated.

The stability of cell-fate decisions regulated by self-activating toggle switches (SATS) depends on TF interactions and external signals. Coupled SATS networks coordinate multiple cellular decisions, offering insights into reprogramming.

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Area of Science:

  • Developmental Biology
  • Systems Biology
  • Synthetic Biology

Background:

  • Cell-fate decisions in embryonic development are often controlled by gene regulatory networks.
  • A common motif involves two transcription factors (TFs) with mutual inhibition and self-activation, forming a self-activating toggle switch (SATS).
  • SATS can exhibit three stable states: two differentiated cell fates and one stem-like state.

Purpose of the Study:

  • To investigate the factors governing the stability of three states in individual SATS.
  • To understand how coupled SATS networks coordinate cellular decisions.
  • To provide insights into genetic circuit design and cellular reprogramming.

Main Methods:

  • Mathematical modeling and simulation of SATS dynamics.
  • Analysis of TF self-activation, mutual inhibition, and degradation rates.
  • Investigation of external signal influences on SATS states.
  • Examination of coupled SATS network behavior.

Main Results:

  • The co-existence and relative stability of SATS states are determined by TF self-activation strength, external signals, and mutual degradation rates.
  • These factors also influence the decision-making processes in coupled SATS systems.
  • The study elucidates the operating principles of individual and coupled tristable SATS.

Conclusions:

  • Novel understanding of tristable switches in regulating cellular differentiation.
  • Insights into the design principles for three-way genetic circuits.
  • Potential applications in understanding and engineering cellular reprogramming.