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Asymmetric Division in Muscle Stem Cells Christian Elabd, Ph.D. Joey Pham, B.A. - The muscle system is a model for quiescence (resting) and activity - Satellite cells, or muscle stem cells, can regenerate repeatedly - Satellite cells give rise to myoblasts (mostly), and fibroblasts, adipocytes, chondrocytes. intact muscle intact muscle injured muscle regenerated muscle Histology 2 weeks after injury Hematoxylin and eosin cross section satellite cells myonuclei myofiber Pictures from MJ Conboy, UC Berkeley Muscle System Muscle Regeneration Resting muscle Fiber Quiescent Muscle Stem Cell 1) Activation Myotrauma 2) Proliferation 3) Regeneration Fusion to repair damaged muscle fibers Fusion to produce new muscle fibers Multi-nucleation Self Renewal Return to resting state Symmetry Asymmetry Stem Stem Diff Stem Stem Asymmetric Division = Segregation of DNA, RNA or Proteins in one daughter cell self renewaldifferentiation Symmetric versus Asymmetric Division Satellite SatelliteSatellite = = Myoblast Satellite Dividing Satellite Option 1 Option 2 =Option 3 MyoblastMyoblast + + + Symmetric versus Asymmetric Division in the Context of Muscle HoechstSca-1DesminMerge Differentiated cells are Desmin positive. Non-differentiated cells are Sca-1 positive. Conboy MJ et al. PLoS Biol. 2007 Jul;5(7):e182 Asymmetric Division in the Context of Muscle Summary of Asymmetric Division Hoechst Sca-1 Desmin Merge While most cells in the body divide strictly symmetrically, stem cells have the ability to divide asymmetrically as well. In the context of muscle regeneration, asymmetric division may allow for muscle regeneration without exhausting the pool of satellite cells (or muscle stem cells). Understanding the mechanism of asymmetric division is essential to advancing the control of stem cell self-renewal versus

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