Ex Vivo Trans-differentiation Of Reactive Glial Cells Into Functional Neurons In Organotypic Brain Slices

Major brain disorders are often caused by the loss of functional neurons that leads to brain dysfunction.Therefore,how to effectively regenerate new neurons to restore lost brain functions is the key to treating brain disorders.Our previous work showed that overexpression of a neuronal transcription factor Neuro D1 can efficiently convert astrocytes into functional neurons in the cerebral cortex of stroke mice.And these newly converted neurons can improve the motor functions of the stroke mice.To investigate whether Neuro D1 overexpression can also reprogram astrocytes into functional neurons in human brain tissues,we cultured organotypic slices ex vivo that were surgically removed from epilepsy and glioma patients,and then employed retroviruses or AAV to overexpress Neuro D1 in glial cells.The results demonstrate that ectopic expression of Neuro D1 in human glial cells can regenerate neurons in organotypic slices originated from patients.The study lays the foundation for future clinical application of the Neuro D1 gene therapy to regenerate new neurons in the treatment of brain disorders.