Conversion of human glial cells into neurons in ex vivo culture of human brain tissue: essential roles of the transcription factors NeuroD1 and Ascl1

Transcription factor–mediated cell conversion has been reported in the central nervous system of both rodents and nonhuman primates. In particular, glia-to-neuron conversion has been achieved in the brain and spinal cord of animal models for neural regeneration and repair. However, whether glia-to-neuron conversion can be used for brain repair in humans needs to be explored. To investigate the use of glia-to-neuron conversion technology in the human brain, we established a long-term ex vivo culture system using human brain tissue that was surgically removed from epileptic patients to test glia-to-neuron conversion directly. We found that neural transcription factors NeuroD1 and Ascl1 both converted human glial cells into neurons. Immunostaining and electrophysiological recordings showed that the glia-converted neurons demonstrated immature properties during the initial 7–14 days of conversion, and then acquired more mature neuronal properties after 21–27 days of conversion. These ex vivo conversion studies in human brain tissue pave the way toward future clinical trials using a transcription factor-based glia-to-neuron conversion approach to treat neurological disorders.