Conditional removal of N-cadherin and M-cadherin in mice leads to a break in muscle stem cell quiescence and long-term expansion of a regeneration-proficient pool via beta-catenin.
Does the conditional removal of N-cadherin and M-cadherin induce a quiescence-to-activation transition in muscle stem cells in mice?
Niche cadherins (N-cadherin and M-cadherin) control the quiescence-to-activation transition in muscle stem cells, with their removal leading to stem cell activation and expansion.
Many adult stem cells display prolonged quiescence, promoted by cues from their niche. Upon tissue damage, a coordinated transition to the activated state is required because non-physiological breaks in quiescence often lead to stem cell depletion and impaired regeneration. Here, we 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 toward full activation. Among these is nuclear localization of β-catenin, which is necessary for this phenotype. Injury-induced perturbation of niche adhesive junctions is therefore a likely first step in the quiescence-to-activation transition.
Goel et al. (Wed,) conducted a other in Muscle stem cell quiescence and activation. Conditional removal of N-cadherin and M-cadherin was evaluated on Break in SC quiescence and long-term expansion of a regeneration-proficient SC pool. Conditional removal of N-cadherin and M-cadherin in mice leads to a break in muscle stem cell quiescence and long-term expansion of a regeneration-proficient pool via beta-catenin.