Unbalanced response to growth variations reshapes the cell fate decision landscape
Jingwen Zhu1, Pan Chu1,2, Xiongfei Fu3,4
1CAS Key Laboratory for Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Nature Chemical Biology
|March 24, 2023
Summary
Cell growth rate significantly impacts gene networks and cell-fate decisions. Our study reveals how growth variations alter the stability of gene expression landscapes, influencing cell differentiation pathways.
Area of Science:
- Systems Biology
- Synthetic Biology
- Cellular Dynamics
Background:
- Cell growth rate globally influences gene expression, affecting cellular functions.
- Gene networks govern cell-fate decisions, but their stability under varying growth conditions is not fully understood.
Purpose of the Study:
- To investigate how global regulation of cell growth rate affects the stability of gene networks.
- To examine the impact of growth rate variations on the cell-fate decision landscape using a synthetic circuit.
Main Methods:
- Utilized a synthetic circuit based on mutual repression to create a bistable gene expression landscape.
- Employed theoretical modeling and experimental analysis to study the effects of growth rate variations.
Main Results:
- Demonstrated a growth-rate-induced bifurcation in the phenotypic landscape, shifting between monostability and bistability.
- Identified unbalanced gene expression responses to growth variations as the cause of landscape deformation.
- Showed that transitions across the bifurcation point reshape cell-fate determination pathways.
Conclusions:
- Global regulation of cell growth rate is a critical factor in cell-fate determination.
- The stability and dynamics of gene networks are sensitive to cell growth rate variations.
- Understanding growth regulation is essential for predicting and controlling cell-fate decisions.
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