Ascl1 Converts Dorsal Midbrain Astrocytes into Functional Neurons In Vivo
Ascl1 Converts Dorsal Midbrain Astrocytes into Functional Neurons In Vivo
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Ascl1 在体内将背侧中脑星形胶质细胞转化为功能神经元
DOI：
10.1523/jneurosci.3975-14.2015
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发表时间：
2015-06-24
影响因子：
5.3
通讯作者：
Cheng, Leping
中科院分区：
文献类型：
--
作者：
Liu, Yueguang;Miao, Qinglong;Cheng, Leping
在体内，转录因子诱导非神经元细胞分化为神经元为神经再生提供了潜在的治疗途径。尽管在体外和体内已有诱导神经元(IN)细胞产生的报道，但IN细胞是否能完全整合到现有的回路中仍不清楚。在这里，我们表明，在体外和体内，仅表达Achaete-scute Complex Homolog-like 1(Ascl1)就足以将小鼠中脑背侧星形胶质细胞转化为具有细胞功能的细胞。GFAP-腺相关病毒(AAV)载体在星形胶质细胞中的特异性表达可使出生后和成年小鼠背侧中脑、纹状体和体感皮质的星形胶质细胞在体内转化为功能神经元。细胞中的这些细胞逐渐成熟，表现出神经元的形态和标记、动作电位以及来自现有神经元的突触输入和输出。因此，单个转录因子Ascl1足以将脑内星形胶质细胞转化为功能神经元，而GFAP-AAVs是体内星形胶质细胞产生细胞内的有效载体。
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.