Postnatal memory governs cell function in adult skeletal muscle.

Skeletal muscle is the contractile tissue that distributes throughout body, with its functionally heterogeneous properties amongst muscles, which may relate to region specific pathology of muscle diseases. Here we found that homeobox (Hox) genes, key regulators of body-plan in the embryo, are region-specifically and robustly maintained as positional memory in both muscle and its associated stem cells named satellite cells in adult mice and humans. Although satellite cell function in adults was unaffected by genetic loss of Hoxa10 in muscle progenitors at the developmental stage, postnatal deletion of Hoxa10 in satellite cells led to genomic instability and mitosis abnormality, resulting in a remarkable decline in regenerative ability of muscles in a region-specific manner. Our results suggest that Hox-based positional memory is flexibly established during embryonic development and governs topographic function of stem cells in adult muscles once it is fixed, potentially influencing the region-specific weakness in muscle diseases Proliferating satellite cell mRNA profiles of CON (Hoxa10f/f) and scKO (Pax7-CreERT2/+;Hoxa10f/f) were generated by RNA-seq.