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Phys Biol. 2017 Dec 06;15(1):016001. doi: 10.1088/1478-3975/aa90e0.

Cellular reprogramming dynamics follow a simple 1D reaction coordinate.

Physical biology

Sai Teja Pusuluri, Alex H Lang, Pankaj Mehta, Horacio E Castillo

Affiliations

  1. Department of Physics and Astronomy and Nanoscale and Quantum Phenomena Institute, Ohio University, Athens, OH, 45701, United States of America. These authors contributed equally to this work.

PMID: 29211687 PMCID: PMC6482097 DOI: 10.1088/1478-3975/aa90e0

Abstract

Cellular reprogramming, the conversion of one cell type to another, induces global changes in gene expression involving thousands of genes, and understanding how cells globally alter their gene expression profile during reprogramming is an ongoing problem. Here we reanalyze time-course data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple 1D reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of the experimental protocol used. Using Monte-Carlo simulations, we show that such a reaction coordinate emerges from epigenetic landscape models where cellular reprogramming is viewed as a 'barrier-crossing' process between cell fates. Overall, our analysis and model suggest that gene expression dynamics during reprogramming follow a canonical trajectory consistent with the idea of an 'optimal path' in gene expression space for reprogramming.

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