Stem cell fate decisions: Substates and attractors

Area of Science:

• Stem cell biology
• Developmental biology
• Systems biology

Background:

• Gene expression heterogeneity is inherent to stem cell populations.
• Human pluripotent stem cells (hPSCs) can exist in distinct, transient metastable substates.
• These substates impact the cells' potential differentiation pathways.

Purpose of the Study:

• To review findings on hPSC metastable substates.
• To elucidate the dynamic nature and transition mechanisms between these substates.
• To explore the role of deterministic chaos and stochasticity in gene expression dynamics.

Main Methods:

• Review of experimental findings on hPSCs.
• Analysis of single-cell transcriptomics data.
• Modeling of fluorescent marker distributions over time.

Main Results:

• hPSCs occupy distinct metastable substates.
• Substate transitions are dynamic and transient.
• Gene expression dynamics suggest governance by deterministic chaos and stochastic fluctuations.

Conclusions:

• Metastable substates are crucial for understanding hPSC behavior.
• Both deterministic chaos and stochasticity contribute to gene expression dynamics.
• This provides a framework for predicting differentiation outcomes.