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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

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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.

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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.