Myogenic reprogramming of retina-derived cells following their spontaneous fusion with myotubes

Satellite cells are recognized as the main source for myoblasts in postnatal muscle. The possible participation of other cell types in myofiber maintenance remains a subject of debate. Here, we investigated the potential of vascular preparations from mouse retina to undergo myogenesis when cultured alone or with differentiated primary myogenic cultures. The choice of retina, an organ richly supplied with capillary network and anatomically separated from skeletal muscles, ensures that the vasculature preparation is devoid of satellite cells. We demonstrate that retina-derived cells spontaneously fuse with preexisting myotubes and contribute additional myonuclei, some of which initiate expression of muscle-specific genes after fusion. Myogenic differentiation of retinal cells prior to their fusion with preexisting myotubes was not detected. Although originating from vasculature preparations, nuclei undergoing myogenic reprogramming were contributed by cells that were neither endothelial nor blood borne. Our results suggest smooth muscle/pericytes as the possible source, and that myogenic reprogramming depends on the muscle specific transcription factor MyoD. Our studies provide insights into a novel avenue for myofiber maintenance, relying on nuclei of non-myogenic origin that undergo fusion and subsequent myogenic conversion within host myofibers. This process may support ongoing myofiber maintenance throughout life.