Niche Cadherins Control the Quiescence-to-Activation Transition in Muscle Stem Cells

作者：Aviva Goel, Marysia-Kolbe Rieder, Hans-Henning Arnold, Glenn L. Radice, Robert S. Krauss · 发表于：Cell Reports · 年份：2017 · DOI：10.1016/j.celrep.2017.10.102 · 被引用次数：151 · 研究领域：Muscle Physiology and Disorders、Genetics and Physical Performance、Cardiovascular Effects of Exercise

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.