Differentiation of V2a interneurons from human pluripotent stem cells

Significance Spinal cord injury (SCI) significantly disrupts normal neural circuitry, leading to severe degradation of motor and sensory function. Excitatory interneurons that relay signals from the brain to neural networks throughout the spinal cord, including glutamatergic V2a interneurons that coordinate respiration and locomotion, are lost after SCI. Thus, transplantation of V2a interneurons after SCI could provide a novel therapy to restore functional connections between the brain and spared downstream neurons. This study describes the generation of V2a interneurons from human pluripotent stem cells, using developmentally relevant morphogenic signaling pathways. This work provides initial insight into the development of excitatory human interneurons and enables the examination of their therapeutic efficacy for SCI repair.