Reprogramming Study Reveals Single Transcription Factor Ascl1 Converts Astrocytes into Neurons in the Intact Brain

Time:2015-06-26

  A recent study, published in the June 24th issue of the Journal of Neuroscience, demonstrated that expression of a single transcription factor efficiently induced astrocyte-to-neurons conversion in the intact brain.

  Direct conversion of non-neuronal cells into mature neurons in the intact brain offers therapeutic potential for treating neural diseases. Yet, it is still a great challenge to specifically and efficiently convert glial cells, the most abundant cells in the nervous system, into functional neurons in the intact brain. Furthermore, it is poorly understood how the induced neuronal (iN) cells can be fully integrated into existing circuits.

  The authors found that Ascl1 could convert mouse astrocytes into neurons efficiently in vitro. These iN cells exhibited neuronal morphology, expressed neuronal markers, fired action potentials, and form functional synapses. Taking advantage of the astrocyte specific GFAP promoter, the authors then showed that Ascl1 could efficiently convert astrocytes in several brain regions into neurons in vivo. These iN cells could receive synaptic inputs and make output synapses onto preexisting neurons. This work provides a novel approach to obtain functional neurons in the intact brain and a potential therapeutic solution for neural regeneration.

  The paper entitled "Ascl1 converts dorsal midbrain astrocytes into functional neurons in vivo" is published in the June 24th issue of the Journal of Neuroscience. LIU Yueguang and MIAO Qinglong,at the Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, are first authors who contribute equally. Dr. CHENG Leping and Prof. ZHANG Xiaohui are the joint senior authors. 

  This work was supported by grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China, and the Chinese Academy of Sciences.

  

  Transcription factor Ascl1 converts astrocytes into neurons in vivo. (A-D) mCherry expressing cells in control AAV-infected mice had typical astrocytic properties.(E-H) Ascl1-AAV gradually converted astrocytes into neurons in adult mouse brain. (Image by Drs. CHENG Leping and ZHANG Xiaohui’s research groups)

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