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Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells
Dhruv Raina1, Fiorella Fabris2, Luis G Morelli1,2,3
1Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany.
Development (Cambridge, England)
|February 17, 2022
Summary
Embryonic stem cell differentiation involves FGF/ERK signaling dynamics. Researchers observed heterogeneous ERK activity pulses, suggesting signaling near a critical transition point influencing cell fate decisions.
Area of Science:
- Cellular dynamics
- Stem cell biology
- Signal transduction
Background:
- Signal transduction networks control cell fate decisions like differentiation.
- Fibroblast Growth Factor (FGF)/Extracellular signal-Regulated Kinase (ERK) signaling is crucial for pluripotent cell differentiation.
- High time-resolution studies of FGF/ERK signaling dynamics in pluripotent cells are limited.
Purpose of the Study:
- To investigate the dynamic activity of the FGF/ERK signaling network in mouse embryonic stem cells at high temporal resolution.
- To characterize ERK activity patterns in response to defined ligand concentrations and differentiation states.
- To understand how FGF/ERK signaling dynamics contribute to cellular heterogeneity and fate decisions.
Main Methods:
- Utilized live-cell sensors in wild-type and Fgf4-mutant mouse embryonic stem cells.
- Measured dynamic ERK activity at the single-cell level.
- Controlled for defined ligand concentrations and differentiation states.
Main Results:
- Revealed pulsatile ERK activity in single embryonic stem cells.
- Observed heterogeneous pulsing patterns among individual cells.
- Found that consecutive ERK pulse sequences occurred more frequently than predicted by stochastic models.
- Demonstrated that pulse sequences increase with ligand concentration but decrease in more differentiated cells.
Conclusions:
- FGF/ERK signaling in embryonic stem cells operates near a transition point between oscillatory and non-oscillatory dynamics.
- Heterogeneous dynamic signaling contributes to cellular heterogeneity, potentially influencing divergent cell fate decisions.
- Dynamic signaling patterns provide a new layer of information beyond cell state for understanding stem cell behavior.
Keywords:
Cell cycleFGF/ERK signalingMouse embryonic stem cellsOscillationsSignal transduction networksTime series analysis
