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.