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Title: An investiqation of the role of notch3 activity in the requlation of adult skeletal muscle stem cell behaviour
Author: Low, Siew Hui
Awarding Body: University of London
Current Institution: University of London
Date of Award: 2013
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Adult skeletal muscle contains a population of tissue~specific stem cells (satellite cells) that are essential for effective growth, repair and regeneration. Normally maintained in a state of metabolic and proliferative quiescence, satellite cells become activated in response to growth stimuli or damage and proliferate to provide progeny that differentiate to augment, repair or generate new functional muscle fibres. In addition to producing differentiated cells, satellite cells also selfrenew to maintain or replenish the stem cell compartment retain regenerative capacity. The precise mechanism by which this occurs remains uncertain, although seve ral recent studies have implicated the Notch signalling pathway, an evolutionarily conserved system involved in determining cell fate behaviour and fate in a wide range of developing and adult tissues. This thesis presents an investigation of the role of Notch signalling, specifically Notch3 activity, in the regulation of the adult skeletal muscle stem cell phenotype using an in vitro model of satellite cell self-renewal during regeneration. When mouse skeletal muscle precursor cells are induced to differentiate, most form myotubes (immature muscle fibres), whereas a small minority within the same culture adopt a reversible, quiescent, undifferentiated phenotype comparable to that of a satellite cell. This phenotype was shown to be dependent on the expression of the Notch3 receptor and its activation by a specific ligand, Delta-like 4, which is expressed by the nascent myotubes. Furthermore, studies in which isolated reserve cells were reactivated from the quiescent state revealed that Notch3 is rapidly inactivated and subsequently down-regulation prior to re-entry in to the cell cycle, consistent with a role in maintaining the stem cell phenotype. Together, data presented in this thesis suggest that satellite cells can be recruited for differentiation at different stages of activation and how once activated, muscle precursor cells could be sequestered back into a quiescent state during regeneration.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available