The Journal of biological chemistry · 2016
Conversion of Fibroblasts to Parvalbumin Neurons by One Transcription Factor, Ascl1, and the Chemical Compound Forskolin.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Shi Zixiao, Zhang Juan, Chen Shuangquan, Li Yanxin, Lei Xuepei, Qiao Huimin, Zhu Qianwen, Hu Baoyang, Zhou Qi, Jiao Jianwei
Аннотация
Abnormalities in parvalbumin (PV)-expressing interneurons cause neurodevelopmental disorders such as epilepsy, autism, and schizophrenia. Unlike other types of neurons that can be efficiently differentiated from pluripotent stem cells, PV neurons were minimally generated using a conventional differentiation strategy. In this study we developed an adenovirus-based transdifferentiation strategy that incorporates an additional chemical compound for the efficient generation of induced PV (iPV) neurons. The chemical compound forskolin combined with Ascl1 induced ∼80% of mouse fibroblasts to iPV neurons. The iPV neurons generated by this procedure matured 5-7 days post infection and were characterized by electrophysiological properties and known neuronal markers, such as PV and GABA. Our studies, therefore, identified an efficient approach for generating PV neurons.