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Cellular reprogramming dynamics follow a simple 1D reaction coordinate
Sai Teja Pusuluri1,2, Alex H Lang3,4,2, Pankaj Mehta3,4
1Department of Physics and Astronomy and Nanoscale and Quantum Phenomena Institute, Ohio University, Athens, OH, 45701, United States of America.
Physical Biology
|December 7, 2017
Summary
Cellular reprogramming to induced pluripotent stem cells (iPSCs) follows a single, universal gene expression path. This optimal trajectory is independent of experimental methods or time, simplifying our understanding of cell fate changes.
Area of Science:
- Cellular and Molecular Biology
- Developmental Biology
- Systems Biology
Background:
- Cellular reprogramming involves global gene expression changes, crucial for converting cell types.
- Understanding the dynamics of these gene expression alterations during reprogramming is a significant challenge.
Purpose of the Study:
- To analyze gene expression dynamics during cellular reprogramming to induced pluripotent stem cells (iPSCs).
- To identify a unifying principle governing gene expression changes across different reprogramming protocols and timelines.
Main Methods:
- Reanalysis of time-course data from cellular reprogramming experiments.
- Application of dimensionality reduction techniques to identify key gene expression trajectories.
- Monte Carlo simulations based on epigenetic landscape models.
Main Results:
- Gene expression dynamics during reprogramming follow a simple, one-dimensional (1D) reaction coordinate.
- This coordinate is invariant to the duration of reprogramming and specific experimental protocols.
- Simulations support a 'barrier-crossing' model where reprogramming follows an optimal path.
Conclusions:
- Cellular reprogramming exhibits a canonical gene expression trajectory, suggesting an underlying optimal path.
- This finding simplifies the complex process of cell fate conversion.
- The identified reaction coordinate provides a fundamental framework for studying reprogramming dynamics.
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