Cell Stem Cell, E-pub Dec. 19, 2013. In Vivo Direct Reprogramming of Reactive Glial Cells into Functional Neurons after Brain Injury and in an Alzheimer’s Disease Model Ziyuan Guo, Lei Zhang, Zheng Wu, Yuchen Chen, Fan Wang, and Gong Chen. http://dx.doi.org/10.1016/j.stem.2013.12.001 Nature Research highlight: http://www.nature.com/nature/journal/v505/n7482/full/505134b.html News press: http://medicalxpress.com/news/2013-12-brain-injury-alzheimer-disease.html Science China (Chinese 中文）： http://www.sciencemagchina.cn/highlights131220.aspx Highlights • Conversion of reactive glial cells into functional neurons in vivo using NeuroD1 • NeuroD1 induces glia-neuron conversion in an Alzheimer’s disease mouse model • NeuroD1 also reprograms NG2 cells into glutamatergic and GABAergic neurons • Human astrocytes can also be converted into glutamatergic neurons with NeuroD1 Summary Loss of neurons after brain injury and in neurodegenerative disease is often accompanied by reactive gliosis and scarring, which are difficult to reverse with existing treatment approaches. Here, we show that reactive glial cells in the cortex of stab-injured or Alzheimer’s disease (AD) model mice can be directly reprogrammed into functional neurons in vivo using retroviral expression of a single neural transcription factor, NeuroD1. Following expression of NeuroD1, astrocytes were reprogrammed into glutamatergic neurons, while NG2 cells were reprogrammed into glutamatergic and GABAergic neurons. Cortical slice recordings revealed both spontaneous and evoked synaptic responses in NeuroD1-converted neurons, suggesting that they integrated into local neural circuits. NeuroD1 expression was also able to reprogram cultured human cortical astrocytes into functional neurons. Our studies therefore suggest that direct reprogramming of reactive glial cells into functional neurons in vivo could provide an alternative approach for repair of injured or diseased brain.
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