Fig. 6: Magnetic delivery of NT-MAG-Exomyo determines anti-inflammatory polarization of muscle-infiltrating macrophages and muscle reprogramming in mdx mice.

Transcriptomic analysis of freshly FACS-purified circulating macrophages that infiltrated hind limb muscle tissues and entrapped CFSE+ exosomes (Ly6ChiCFSEhi; iMAC) in non-magnetic NT-Exomyo III (n = 3) and magnetic NT-MAG-Exomyo III (n = 3) mice (upper panel, a–d). Transcriptomic analysis of single muscle fibres (MS) from the hind limb muscle tissues from non-magnetic NT-Exomyo III (n = 3), and magnetic NT-MAG-Exomyo III (n = 3) mice (bottom panel, e–h). Mdx mice systemically injected with PBS were used as controls (vehicle, n = 3). a,e, Heatmap of Euclidean distances between log2 counts per million gene expression values across all macrophage samples (a) and myofibres (e). The colour scale ranges from 0 (indicating identical gene expression) in red to 400 (indicating the highest distance) in blue. b,f, Heatmap of log CPM expression values for the top 100 differentially expressed genes (DEGs) between groups, for muscle infiltrating macrophages (b) and myofibres (f). The colour scale ranges from low expression (blue) to high expression (red). Expression values were standardized. c,g, Venn diagram of the shared DEGs between groups, for muscle infiltrating macrophages (c) and myofibres (g). d,h, GO pathway analysis of upregulated (left) and downregulated (right) genes in muscle infiltrating macrophages (d) and myofibres (h). A one-sided version of Fisher’s exact test was used to determine whether known biological functions or processes are overrepresented in the list of differentially expressed genes. The P values are adjusted according to the Benjamini–Hochberg method. P value and q value cut-offs are 0.01 and 0.05, respectively. The size of each dot is proportional to the number of genes in the corresponding category. The colour scale represents the significance of the analysis for each category: red denotes higher significance; blue denotes lower significance.