Victor Olariu
Senior lecturer
A quantitative model of cellular decision making in direct neuronal reprogramming
Author
Summary, in English
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. We found that nPTB needs to feed back into the direct neural conversion network most likely via PTB in order to accurately capture quantitative gene interaction dynamics and correctly predict the outcome of various overexpression and knockdown experiments. This was experimentally validated by nPTB knockdown leading to successful neural conversion. We also proposed 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.
Department/s
- Computational Biology and Biological Physics - Has been reorganised
Publishing year
2021-01-15
Language
English
Publication/Series
Scientific Reports
Volume
11
Issue
1
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Bioinformatics and Systems Biology
- Neurology
- Other Physics Topics
Keywords
- direct reprogramming
- neuron
- fibroblast
- PTB
- nPTB
- miR-124
- REST
Status
Published
Project
- Computational Science for Health and Environment
- Modelling cellular decision making in direct reprogramming to neurons
ISBN/ISSN/Other
- ISSN: 2045-2322