Generation of self-renewing neuromesodermal progenitors with neuronal and skeletal muscle bipotential from human embryonic stem cells

Progress has been made in generating spinal cord and trunk derivatives from neuromesodermal progenitors (NMPs). However, maintaining the self-renewal of NMPs in vitro remains a challenge. In this study, we developed a cocktail of small molecules and growth factors that induces human embryonic stem cells to produce self-renewing NMPs (srNMPs) under chemically defined conditions. These srNMPs maintain the state of thoracic neuromesodermal progenitors in prolonged culture and have the bipotential to generate mesodermal cells and neurons, even at the single-cell level. Additionally, suspended srNMP aggregates could partially mimic the structural properties of early embryonic trunks. Furthermore, transplanted srNMP-derived muscle satellite cells or progenitors of motor neurons were integrated into skeletal muscle or the spinal cord, respectively, and contributed to regeneration in mouse models. In summary, srNMPs hold great promise for applications in developmental biology and as renewable cell sources for cell therapy for trunk and spinal cord injuries.