Transcriptional Dynamics of the Embryonic Stem Cell Switch
Author Information
Author(s): Chickarmane Vijay, Troein Carl, Nuber Ulrike A, Sauro Herbert M, Peterson Carsten
Primary Institution: Keck Graduate Institute, Claremont, California, United States of America
Hypothesis
How are embryonic stem cells regulated at the genetic level?
Conclusion
The study identifies a bistable switch in the transcriptional regulatory network of embryonic stem cells that determines their fate between self-renewal and differentiation.
Supporting Evidence
- The study elucidates the architecture of the transcriptional regulatory circuitry responsible for cell determination.
- Positive feedback loops in the network lead to bistable switch behavior.
- The model predicts that increasing the binding strength of NANOG to OCT4 and SOX2 can lead to an irreversible bistable switch.
Takeaway
This study shows that embryonic stem cells can switch between staying the same and changing into different types of cells based on certain signals, like a light switch.
Methodology
The authors used a kinetic modeling approach to analyze the interactions between transcription factors OCT4, SOX2, and NANOG in embryonic stem cells.
Limitations
The model does not account for the effects of overexpression of OCT4 and NANOG on differentiation.
Digital Object Identifier (DOI)
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