<p> 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. </p><p>
| Identifer | oai:union.ndltd.org:PROQUEST/oai:pqdtoai.proquest.com:10743988 |
| Date | 28 February 2018 |
| Creators | Goel, Aviva J. |
| Publisher | Icahn School of Medicine at Mount Sinai |
| Source Sets | ProQuest.com |
| Language | English |
| Detected Language | English |
| Type | thesis |
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