In adult mammals, satellite cells serve as muscle stem cells that contribute to myofiber repair and homeostasis. Previous work has shown that the ablation of satellite cells impairs muscle regeneration after injury, but does not impact homeostasis, suggesting additional cell populations may contribute to muscle tissue maintenance. Now, Deneen Wellik and colleagues use genetic labelling and lineage tracing techniques to reveal that a subpopulation of Hox-expressing interstitial stromal cells contributes to adult muscle homeostasis. The authors use Hoxa11 reporters to show that Hoxa11 expression is maintained in muscle interstitial cells from early embryonic stages through adulthood. Using rigorous immunofluorescent co-labelling, the researchers show that Hoxa11-expressing cells do not overlap with haematopoietic, endothelial or satellite cells. Crucially, the Hoxa11 lineage does not label or transit through satellite cell populations. Although the Hoxa11 lineage does not contribute to muscle tissue in embryos, in vivo and in vitro experiments show that Hoxa11-positive cells progressively and directly contribute to muscle myofibers beginning at postnatal stages. In response to injury in vivo, Hoxa11-lineage cells do not contribute to myofibers until the repair has progressed to new myofiber formation. Together these data build upon growing evidence that satellite cell-independent sources generate muscle tissue in vivo.
