Ascl1 Converts Dorsal Midbrain Astrocytes into Functional Neurons In Vivo

作者：Liu, Yueguang; Miao, Qinglong; Yuan, Jiacheng; Han, Su'e; Zhang, Panpan; Li, Sanlan; Rao, Zhiping; Zhao, Wenlong; Ye, Qian; Geng, Junlan; Zhang, Xiaohui; Cheng, Leping^*

来源：Journal of Neuroscience, 2015, 35(25): 9336-9355.

DOI：10.1523/JNEUROSCI.3975-14.2015

• astrocyte-to-neuron conversion in vivo
• cell fate determination
• induced neuronal (iN) cells
• proneural gene Ascl1
• transdifferentiation

In vivo induction of non-neuronal cells into neurons by transcription factors offers potential therapeutic approaches for neural regeneration. Although generation of induced neuronal (iN) cells in vitro and in vivo has been reported, whether iN cells can be fully integrated into existing circuits remains unclear. Here we show that expression of achaete-scute complex homolog-like 1 (Ascl1) alone is sufficient to convert dorsal midbrain astrocytes of mice into functional iN cells in vitro and in vivo. Specific expression of Ascl1 in astrocytes by infection with GFAP-adeno-associated virus (AAV) vector converts astrocytes in dorsal midbrain, striatum, and somatosensory cortex of postnatal and adult mice into functional neurons in vivo. These iN cells mature progressively, exhibiting neuronal morphology and markers, action potentials, and synaptic inputs from and output to existing neurons. Thus, a single transcription factor, Ascl1, is sufficient to convert brain astrocytes into functional neurons, and GFAP-AAVis an efficient vector for generating iN cells from astrocytes in vivo.

• 出版日期2015-6-24
• 单位中国科学院上海生命科学研究院; 北京师范大学; 神经科学国家重点实验室; 中国科学院大学; 认知神经科学与学习国家重点实验室