A Quantitative Model of Cellular Decision Making in Direct Neuronal Reprogramming [article]

Adriaan Merlevede, Viktor Drugge, Roger A. Barker, Janelle Drouin-Ouellet, Victor Olariu
2020 bioRxiv   pre-print
The direct reprogramming of adult skin fibroblasts to neurons is thought to be controlled by a small set of interacting gene regulators. Here, we investigate how the interaction dynamics between these regulating factors coordinate cellular decision making in direct neuronal reprogramming. We put forward a quantitative model of the governing gene regulatory system, supported by measurements of mRNA expression level dynamics. We find that reinterpreting the interaction between two genes (PTB and
more » ... two genes (PTB and nPTB) is necessary to capture quantitative gene interaction dynamics and correctly predict the outcome of various overexpression and knockdown experiments. This analysis is strengthened by a novel analytical technique to dissect system behaviour and reveal the influence of individual factors on resulting gene expression. Overall, we demonstrate that computational analysis is a powerful tool for understanding the mechanisms of direct (neuronal) reprogramming, paving the way for future models that can help improve cell conversion strategies.
doi:10.1101/2020.02.04.933713 fatcat:66y5mlorurcj5mngaf7vcplfry