The Skeletal Muscle Stem Cell Niche: Defining Hierarchies Based upon the Stem Cell Marker Pw1 to Identify Therapeutic Target Cells

.......................................................................................................................... 13 RÉSUMÉ DE LA THÈSE ........................................................................................................ 14 CHAPTER 1. THE SKELETAL MUSCLE NEIGHBORHOOD ................................................. 23 1. Generalities about skeletal muscle ................................................................................................25 1.1. Skeletal muscle structure and function ...............................................................................25 1.2. Embryonic development of vertebrate limb skeletal muscles ...................................27 2. Postnatal skeletal muscle stem cells .............................................................................................33 2.1. The satellite cell ............................................................................................................................33 2.2. Non-satellite muscle progenitors .........................................................................................39 3. Influence of the niche on stem cell behavior .............................................................................42 3.1. “External” signals: the action of inflammatory cells .......................................................42 3.2. “Internal” signals: the myogenic/adipogenic balance ...................................................45 CHAPTER 2. MECHANISMS REGULATING SKELETAL MUSCLE MASS ........................... 49 1. Changes in muscle mass throughout life ....................................................................................51 1.1. Muscle hypertrophy during postnatal growth and physical training ......................51 1.2. Age and disease-related loss of muscle mass ..................................................................55 2. The major signaling pathways regulating muscle size ...........................................................59 2.1. Myostatin, a potent inhibitor of muscle mass ..................................................................59 2.2. Myostatin non-canonical pathways .....................................................................................65 2.3. A myostatin endogenous antagonist: follistatin ..............................................................67 te l-0 08 33 42 2, v er si on 1 12 J un 2 01 3