Heterogeneity within the muscle stem cell population reflects a Notch-driven response to macrophages

Description

Abstract Muscle stem cells (muSCs) are crucial for muscle repair, but are increasingly understood to represent a heterogenous population with different regenerative potentials and responses to regulatory signals. To investigate how heterogeneity affects muSC function in vivo we have used zebrafish as a model of tissue regeneration and explored the importance of Notch activity and macrophage function. We show that Notch activity is found in a subset of muSCs that do not show large contributions to focal injury. This response is amplified in an absence of Notch signalling and after ablation of macrophages. In contrast, a population of pax7-expressing muSCs require Notch activity for their expansion after injury and are negatively regulated by macrophages. Manipulation of Notch in macrophages reveals a macrophage-dependent activation of Notch differentially regulates these two muSC populations to ensure robustness in response to tissue injury.

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