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Fetal myoblast clones contribute to both fast and slow fibres in developing rat muscle
1MRC Muscle and Cell Motility Unit and Developmental Biology Research Centre, The Randall Institute, King's College London, United Kingdom. simon.hughes@kcl.ac.uk
Insights
Retroviral cell marking reveals that muscle stem cell clones contribute to both slow and fast muscle fiber types during development. This suggests developmental plasticity in muscle fiber fate determination.
Area of Science:
- Developmental Biology
- Muscle Physiology
- Cell Biology
Background:
- Understanding muscle development is crucial for regenerative medicine.
- Cell lineage tracing provides insights into cell fate determination.
- Myoblast differentiation contributes to muscle fiber formation.
Purpose of the Study:
- To investigate the role of cell lineage in fetal and neonatal rat muscle development.
- To determine the contribution of myoblast clones to different muscle fiber types.
- To explore the potential of retroviral vectors for muscle-specific gene delivery.
Main Methods:
- Retroviral cell lineage marking in fetal and neonatal rats.
- Analysis of infected cell clusters and their contribution to muscle fibers.
- Assessment of retroviral gene expression in muscle and non-muscle tissues.
Main Results:
- Clusters of infected cells, presumed myoblast clones, contribute to both slow primary and fast secondary muscle fibers.
- Single myoblast clones can contribute to both slow-twitch and fast-twitch muscle fibers, indicating plasticity.
- High infection efficiency of muscle fibers in fetal rats using a self-inactivating retroviral vector.
- Markedly lower retroviral gene expression in non-muscle tissues suggests muscle-targeting potential.
Conclusions:
- Single myoblast clones exhibit plasticity, contributing to diverse muscle fiber types during development.
- Fetal retroviral infection can potentially target exogenous genes to mammalian muscle fibers.
- This study provides a foundation for understanding muscle development and gene therapy applications.
Abstract:
Retroviral cell lineage marking was used to investigate the role of cell lineage in fetal and neonatal rat muscle development. Clusters of infected cells, presumably myoblast clones, contribute cells to both slow primary and fast secondary fibres. Moreover, single clusters of marked cells contain both slow and fast primary fibres, suggesting that, at least during fetal life, single clones contribute nuclei to both fibres that are committed to remain slow and those that convert to a fast phenotype. The majority of fibres in individual fascicles of fetal muscle could be infected by a self-inactivating retroviral vector. Retroviral gene expression was markedly lower in non-muscle tissues, suggesting that fetal retroviral infection might target exogenous genes to mammalian muscle fibres during later life.