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Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans
Published on: February 16, 2017
Using computer simulation models to investigate the most promising microRNAs to improve muscle regeneration during
Carole J Proctor1, Katarzyna Goljanek-Whysall2
1MRC/Arthritis Research UK Centre for Musculoskeletal Ageing (CIMA), Institute of Cellular Medicine and Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK. carole.proctor@ncl.ac.uk.
Abstract:
MicroRNAs (miRNAs) regulate gene expression through interactions with target sites within mRNAs, leading to enhanced degradation of the mRNA or inhibition of translation. Skeletal muscle expresses many different miRNAs with important roles in adulthood myogenesis (regeneration) and myofibre hypertrophy and atrophy, processes associated with muscle ageing. However, the large number of miRNAs and their targets mean that a complex network of pathways exists, making it difficult to predict the effect of selected miRNAs on age-related muscle wasting. Computational modelling has the potential to aid this process as it is possible to combine models of individual miRNA:target interactions to form an integrated network. As yet, no models of these interactions in muscle exist. We created the first model of miRNA:target interactions in myogenesis based on experimental evidence of individual miRNAs which were next validated and used to make testable predictions. Our model confirms that miRNAs regulate key interactions during myogenesis and can act by promoting the switch between quiescent/proliferating/differentiating myoblasts and by maintaining the differentiation process. We propose that a threshold level of miR-1 acts in the initial switch to differentiation, with miR-181 keeping the switch on and miR-378 maintaining the differentiation and miR-143 inhibiting myogenesis.
Insights
This study models microRNA (miRNA) interactions in muscle regeneration, revealing how specific miRNAs control myogenesis. The findings offer insights into age-related muscle wasting by detailing miRNA roles in muscle cell development.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- MicroRNAs (miRNAs) are crucial regulators of gene expression, impacting cellular processes like muscle regeneration.
- Skeletal muscle development involves complex miRNA networks, but understanding their role in age-related muscle wasting is challenging.
- Existing computational models do not fully capture miRNA:target interactions within muscle tissue.
Purpose of the Study:
- To develop the first computational model of microRNA:target interactions in myogenesis.
- To validate the model using experimental evidence and generate testable predictions.
- To elucidate the specific roles of key miRNAs in regulating muscle cell differentiation and regeneration.
Main Methods:
- Constructed a computational model of miRNA:target interactions based on experimental data.
- Validated individual miRNA interactions within the model.
- Utilized the model to predict miRNA functions in myogenesis.
Main Results:
- The model confirms that miRNAs play essential roles in regulating myogenesis.
- MiRNAs were shown to promote the transition between quiescent, proliferating, and differentiating myoblasts.
- Specific miRNAs (miR-1, miR-181, miR-378, miR-143) were identified with distinct roles in initiating, maintaining, or inhibiting differentiation.
Conclusions:
- The developed model provides a framework for understanding miRNA networks in muscle development.
- MiRNAs are key regulators of the myogenesis process, controlling critical switches in cell fate.
- This research offers potential targets for interventions against age-related muscle wasting by clarifying miRNA functions.
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