GPNMB and Duchenne muscular dystrophy: In this study, we (a) carried out a comprehensive high-dimensional transcriptomic analysis of MF subpopulations in acute and chronic injury models, (b) mapped the spatial distribution of the MF subsets, (c) validated a predicted GFEM marker (GPNMB) and its impact in regeneration, (d) identified ATF3 as a key TF in Gpnmb expression and GFEM regulation, (e) discovered a disease-associated subset that is enriched and present in human DMD pathology, and (f) evaluated the impact of intermittent GC treatment on the newly identified multilayered RIZs.