Forming Embryonic-Like Nervous Tissues and Organs by Muscle-Derived Neuroepithelial Myogenic Progenitors

Abstract

Unlike totipotent ES cells, adult-origin multipotent progenitors have limited differentiation. Several CNS carcinomas featuring embryonic nervous and muscle tissues, however, suggest the existence of distinct primitive progenitors. Rhabdomyosarcoma is a soft tissue malignant tumor, and although it displays phenotypical features of neural and muscle elements, its etiology remains largely unaddressed. It has been shown that muscle-derived neuroepithelial myogenic progenitors (NEMPs) differentiate into radial glial-like cells, neurons, and early myoblasts in vitro and generate embryonic/fetal-like myofibers in vivo. The present study reports that NEMPs could also generate chimeric grafts in muscle, which exhibited morphogenetic features of the embryonic brain, developing nerve nuclei/ganglia, and primitive striated muscle. A single NEMP differentiated in vitro into multiple colonies containing neuroepithelial cells, neurons, astroglia, and myoblasts, with embryonic tissue patterns. The data demonstrate that generation of embryonic nervous tissues is NEMP’s unique potency, providing translational evidence for a NEMP origin of the different malignant neoplasms.