Theoretical modelling discriminates the stochastic and deterministic hypothesis of cell reprogramming

TL;DR

This paper presents a mathematical model to distinguish between stochastic and deterministic hypotheses of cell reprogramming by analyzing reprogramming timing and noise effects, aiding in designing better protocols.

Contribution

The study introduces a general mathematical framework to differentiate reprogramming mechanisms based on timing and noise analysis, which was previously experimentally indistinguishable.

Findings

Noise influences reprogramming time under the stochastic hypothesis.

Reprogramming timing can discriminate between the two hypotheses.

The model is broadly applicable to cell reprogramming studies.

Abstract

How to induce differentiated cells into pluripotent cells has elicited researchers' interests for a long time since pluripotent stem cells are able to offer remarkable potential in numerous subfields of biological research. However, the nature of cell reprogramming, especially the mechanisms still remain elusive for the sake of most protocols of inducing pluripotent stem cells were discovered by screening but not from the knowledge of gene regulation networks. Generally there are two hypotheses to elucidate the mechanism termed as elite model and stochastic model which regard reprogramming process a deterministic process or a stochastic process, respectively. However, the difference between these two models cannot yet be discriminated experimentally. Here we used a general mathematical model to elucidate the nature of cell reprogramming which can fit both hypotheses. We investigated this process from a novel perspective, the timing. We calculated the time of reprogramming in a general way and find that noise would play a significant role if the stochastic hypothesis holds. Thus the two hypotheses may be discriminated experimentally by counting the time of reprogramming in different magnitudes of noise. Because our approach is general, our results should facilitate broad studies of rational design of cell reprogramming protocols.