The Muscle Stem Cell Niche in Health and Disease

The regulation of stem cells that maintain and regenerate postnatal tissues depends on extrinsic signals originating from their microenvironment, commonly referred to as the stem cell niche. Complex higher-order regulatory interrelationships with the tissue and factors in the systemic circulation are integrated and propagated to the stem cells through the niche. The stem cell niche in skeletal muscle tissue is both a paradigm for a structurally and functionally relatively static niche that maintains stem cell quiescence during tissue homeostasis, and a highly dynamic regenerative niche that is subject to extensive structural remodeling and a flux of different support cell populations. Conditions ranging from aging to chronically degenerative skeletal muscle diseases affect the composition of the niche and thereby impair the regenerative potential of muscle stem cells. A holistic and integrative understanding of the extrinsic mechanisms regulating muscle stem cells in health and disease in a broad systemic context will be imperative for the identification of regulatory hubs in the niche interactome that can be targeted to maintain, restore, or enhance the regenerative capacity of muscle tissue. Here, we review the microenvironmental regulation of muscle stem cells, summarize how niche dysfunction can contribute to disease, and discuss emerging therapeutic implications.