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Brn2 单独足以将星形胶质细胞转化为神经祖细胞和神经元。

Brn2 Alone Is Sufficient to Convert Astrocytes into Neural Progenitors and Neurons.

机构信息

1 Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology , Kunming, Yunnan, China .

2 Faculty of Environmental Science and Engineering, Kunming University of Science and Technology , Kunming, Yunnan, China .

出版信息

Stem Cells Dev. 2018 Jun 1;27(11):736-744. doi: 10.1089/scd.2017.0250. Epub 2018 May 15.

Abstract

Generating neurons or neural progenitor cells (NPCs) from astrocytes is a potential strategy for neurological repair by reprogramming. Previous study has showed that Brn2, by cooperating with other factors, participates in neurogenesis and neuronal reprogramming. However, it is still unclear whether the Brn2 alone can convert astrocytes into neurons or NPCs. Here, we explored the effect of Brn2 on reprogramming of astrocytes, and found that a single transcription factor Brn2 can convert mouse astrocytes into functional neurons. Furthermore, the Brn2-infected astrocytes can be induced into NPCs after changing culture condition. In addition, our study found that the reprogramming of astrocytes and the fate of transdifferentiated cells are closely associated with cell microenvironmental factors, such as the brain regions where the astrocytes come from, the proliferation ability of astrocytes, and culture condition of infected astrocytes. To sum up, for the first time, our results demonstrated that Brn2 alone is sufficient to convert astrocytes into neural progenitors and neurons, and the conversion is associated with cell microenvironments. This new conversion method will be a potential therapeutic approach to restore the injured diseased brain in regenerative medicine.

摘要

从星形胶质细胞中产生神经元或神经祖细胞(NPC)是通过重编程进行神经修复的一种潜在策略。先前的研究表明,Brn2 通过与其他因素合作,参与神经发生和神经元重编程。然而,目前尚不清楚 Brn2 是否可以单独将星形胶质细胞转化为神经元或 NPC。在这里,我们研究了 Brn2 对星形胶质细胞重编程的影响,发现单个转录因子 Brn2 可以将小鼠星形胶质细胞转化为功能性神经元。此外,改变培养条件后,感染 Brn2 的星形胶质细胞可以被诱导为 NPC。此外,我们的研究发现,星形胶质细胞的重编程和转分化细胞的命运与细胞微环境因素密切相关,例如星形胶质细胞来自的脑区、星形胶质细胞的增殖能力以及感染星形胶质细胞的培养条件。总之,我们的研究结果首次表明,Brn2 单独足以将星形胶质细胞转化为神经祖细胞和神经元,并且这种转化与细胞微环境有关。这种新的转化方法将成为再生医学中恢复受损病变大脑的潜在治疗方法。

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