Many adult stem cells are characterized by prolonged quiescence, promoted by cues from their niche. Upon tissue damage, a coordinated transition to the activated state is necessary for successful repair. Non-physiological breaks in quiescence often lead to stem cell depletion and impaired tissue restoration. Here, I identify cadherin-mediated adhesion and signaling between muscle stem cells (satellite cells; SCs) and their myofiber niche as a mechanism that orchestrates the quiescence-to-activation transition. Conditional removal of N-cadherin and M-cadherin in mice leads to a break in SC quiescence with long-term expansion of a regeneration-proficient SC pool. These SCs have an incomplete disruption of the myofiber-SC adhesive junction, and maintain niche residence and cell polarity, yet show properties of SCs in a state of transition from quiescence towards full activation. Among these properties is nuclear localization of b- catenin, which is necessary for this phenotype. These findings are consistent with the conclusion that injury-induced perturbation of niche adhesive junctions is a first step in the quiescence-to-activation transition.
|Advisor:||Krauss, Robert S.|
|Commitee:||Chess, Andrew, Kardon, Gabrielle, Mlodzik, Marek, Soriano, Philippe|
|School:||Icahn School of Medicine at Mount Sinai|
|Department:||Developmental and Stem Cell Biology|
|School Location:||United States -- New York|
|Source:||DAI-B 79/05(E), Dissertation Abstracts International|
|Subjects:||Biology, Molecular biology, Genetics|
|Keywords:||Cadherin, Muscle, Niche, Quiescence, Regeneration, Stem cell|
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