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Table of contents
INTRODUCTION
Chapter 1. Skeletal muscle and its resident stem cells
1. Skeletal muscle structure and function
1.1. Skeletal muscle as a contractile unit
1.2. Muscle regeneration
2. Satellite cells as adult skeletal muscle stem cells
2.1. A brief history
2.2. Molecular regulation of muscle stem cell emergence
2.3. Heterogeneity in the muscle stem cell population
3. Functions of muscle stem cells
3.1. Adult myogenesis
3.1.1. Satellite cell activation and differentiation
3.1.2. Satellite cell self-renewal
Chapter 2. Stem cell niche is essential for quiescence
1. Stem cell quiescence
1.1. Identification of quiescent stem cells
1.2. Ex vivo induction of quiescence
1.3. Molecular signature of quiescence
1.3.1. Epigenetic control
1.3.2. Cell cycle regulators
2. Molecular signature of MuSCs
2.1.1. Calcitonin receptor
2.1.2. Teneurin-4 or Odz4
2. The stem cell niche
2.1. Extracellular matrix: powerful modulator of cell behaviour
2.2. ECM-cell interaction
2.3. Biophysical properties of ECM
2.4. Collagens constitute a major component of the ECM
2.4.1. Insights from Collagen V
3. The MuSCs niche
3.1. Extracellular matrix and associated factors
Chapter 3. Post-transcriptional regulation of myogenesis: a role for microRNAs
1. The discovery of microRNAs
2. MicroRNAs: Genomics, biogenesis, mechanism and function
2.1. Biogenesis of microRNAs
2.2. MicroRNAs arise from distinct genomic loci
2.3. MicroRNA prediction tools
3. MicroRNAs in cell and tissue regulation
4. Regulation of myogenesis by microRNAs
5. Inhibition of microRNAs using “Antagomirs”
Chapter 4. Notch signalling is a pleiotropic regulator of stem cells
1. An introduction to the world of Notch
2. Notch receptors, ligands and the cascade
3. Notch targets genes and their regulation
4. Notch signalling in the regulation of stem cell fate
5. Notch signalling in skeletal muscle and satellite cells
RESULTS
Part I: Notch-induced Collagen V maintains muscle stem cells by reciprocal activation of the Calcitonin Receptor
Part II: The Notch-induced microRNA-708 maintains quiescence and regulates migratory behavior of adult muscle stem cells
CONCLUSIONS AND PERSPECTIVES
1. Context of this thesis project
2. Notch signalling regulates ECM niche components
3. Notch signalling positions MuSCs in their niche
4. Potential regulation of Notch signalling by microRNAs
ANNEX 1: Review Regulation and phylogeny of muscle regeneration
ANNEX 2: Resource paper Comparison of multiple transcriptomes using a new analytical pipeline Sherpa exposes unified and divergent features of quiescent and activated skeletal muscle stem cells
ANNEX 3: Small-RNA sequencing identifies dynamic microRNA deregulation during muscle lineage progression
REFERENCES




