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Molecular noise modulates transitions in the cell-fate differentiation landscape
Yujing Liu1, Adriana Zanca1,2, Michael P H Stumpf3,4,5
1School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, Australia.
NPJ Systems Biology and Applications
|June 21, 2026
Summary
Molecular noise significantly alters biological system transition paths, diverging from deterministic models. Stochastic dynamics reveal novel reaction pathways not predicted by traditional least-action principles.
Area of Science:
- Systems biology
- Theoretical biology
- Computational biology
Background:
- Waddington's epigenetic landscape is a key metaphor for cell-type determination.
- Molecular noise can reshape epigenetic landscapes.
- The impact of noise on transitions between landscape valleys remains unclear.
Purpose of the Study:
- To investigate how noise affects transition paths in dynamic epigenetic landscapes.
- To compare stochastic transition paths with deterministic least-action paths.
Main Methods:
- Analysis of illustrative exemplars of non-equilibrium systems.
- Dissection of system dynamics under stochastic conditions.
- Calculation of reactive density and transition currents.
Main Results:
- Noise generates transition paths that substantially differ from deterministic least-action paths.
- Stochastic dynamics lead to non-trivial divergence from simple barrier crossing models.
- Reactive density and transition currents reveal specific locations and mechanisms of stochastic transitions.
Conclusions:
- Noise profoundly alters transition paths in epigenetic landscapes.
- Deterministic models are insufficient for accurately describing stochastic transitions.
- Understanding noise-driven dynamics is crucial for cell fate and developmental biology.
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