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Table of contents
List of tables
List of abbreviations
Summary
Zusammenfassung
Résumé
1. General introduction
1.1 Muscle tissue
1.1.1 Muscle development
1.2 Muscle stem cells (MuSCs)
1.2.1 Characterization of MuSCs
1.2.2 Human satellite cells
1.3 The stem cell niche
1.3.1 Regulatory signaling pathways
1.3.2 The satellite cell niche
1.4 Notch signaling
1.4.1 Notch ligands and receptors
1.4.2 Notch determines asymmetric division
1.4.3 Multiple roles of Notch in cells of the myogenic lineage
1.4.4 Notch signaling in satellite cells
1.5 Muscle stem cells for cell therapy
1.5.1 DMD model and treatment
1.5.2 Cell therapy
1.5.3 Isolation of MuSCs
1.5.4 Adeno-associated virus (AAV)
2. Aim of the Project
3. Materials and methods
3.1 Materials
3.1.1 Chemicals and consumables
3.1.2 Plasmids and cell lines
3.1.3 Animals
3.1.4 Antibodies
3.1.5 Buffers, solutions and media
3.1.6 Software
3.2 Methods
3.2.1 Molecular biological methods
3.2.2 Cell biology Methods
3.2.3 Biochemical methods
3.2.4 Histological methods
3.2.5 Transgenic animal experiments
3.2.6 Statistical analysis
4. Results
4.1 Fiber-associated satellite cell culture
4.2 Recombinant Dll1-Fc protein production
4.3 The biological effect of Dll1-Fc on cultured myoblasts
4.4 The effect of Dll1-Fc on muscle progenitor cells (MPCs)
4.5 The in vivo effect of Notch overstimulation
4.5.1 The viral gene transfer system
4.5.2 The effect of Notch overstimulation on postnatal muscle growth
4.5.3 The effect of Dll1-overexpression during muscle regeneration
5. Discussion
5.1 Immobilization of Dll1-Fc and its effect in myoblasts.
5.1.1 Dll1-Fc stimulation suppresses myoblast differentiation.
5.1.2 The effect of Dll1-Fc on myoblast proliferation.
5.2 The ex vivo cultivation of muscle stem cells.
5.2.1 Notch stimulation impairs proliferation of cultured MPCs
5.2.2 Notch stimulation via Dll1-Fc preserves stemness in cultured MPCs.
5.3 Overexpression of Dll1 in vivo
5.3.1 Overexpression of Dll1 in wild-type mice during muscle development
5.4 Outlook
6. Bibliography
7. Appendix
7.1 Copyright permissions
7.2 Own Publication
8. Acknowledgement
