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bioRxiv · 10.1101/257220

Quantifying Waddington’s epigenetic landscape: a comparison of single-cell potency measures

Shi, J.·Teschendorff, A.·Chen, W.·Chen, L.·Li, T.
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Abstract

Over 60 years ago Waddington proposed an epigenetic landscape model of cellular differentiation, whereby cell-fate transitions are modelled as canalization events, with stable cell states occupying the basins or attractor states1, 2. A key ingredient of this landscape is the energy potential, or height3, which correlates with cell-potency. To date, very few explicit biophysical models for estimating single-cell potency have been proposed. Using 9 independent experiments, encompassing over 6,600 high-quality single-cell RNA-Seq profiles, we here demonstrate that single-cell potency can be approximated as the graph entropy of a Markov Chain process on a model signaling network. Our analysis highlights that other proposed single-cell potency measures are not robust, whilst also revealing that integration with orthogonal systems-level information improves potency estimates. Thus, this study provides a foundation for an improved systems-level understanding of single-cell potency, which may have profound implications for the discovery of novel stem-and progenitor cell phenotypes.

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Shi, J., Teschendorff, A., Chen, W., Chen, L., Li, T.. 2018-01-30. Quantifying Waddington’s epigenetic landscape: a comparison of single-cell potency measures. https://doi.org/10.1101/257220

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