中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (1): 25-32.doi: 10.4103/1673-5374.125326

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

Mash1能有效重编程大鼠星形胶质细胞为神经元

  

  • 收稿日期:2013-11-25 出版日期:2014-01-05 发布日期:2014-01-05
  • 基金资助:

    国家重点基础研究发展计划(973计划)(2010CB530400);国家自然科学基金重点项目(30930111)

Mash1 efficiently reprograms rat astrocytes into neurons

Daofang Ding1, 2, Leqin Xu1, 2, Hao Xu1, 2, Xiaofeng Li1, 2, Qianqian Liang1, 2, Yongjian Zhao1, 2, Yongjun Wang1, 2   

  1. 1 Institute of Spine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    2 Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • Received:2013-11-25 Online:2014-01-05 Published:2014-01-05
  • Contact: Yongjun Wang, M.D., Ph.D., Institute of Spine, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China, yjwang88@hotmail.com.
  • Supported by:

    This study was supported by the National Basic Research Program of China (973 Program), No. 2010CB530400; the Key Project of National Natural Science Foundation of China, No. 30930111. 

摘要:

和神经元细胞来源不同胚层的成纤维细胞在转录因子Mash1和Brn2作用下即可转变成神经元,而对于和神经元来自于同一胚层的胶质细胞,是否更容易转变成神经元?为此,实验提取2月龄SD大鼠的星形胶质细胞,发现Brn2可在星形胶质细胞中内源性表达,而无Mash1的表达。因此进一步推测仅仅Mash1基因即可实现胶质细胞向神经元的转变。实验将MSCV-MASH1重组质粒导入星形胶质细胞后72h,所有细胞表达Mash1;导入后1周,星形胶质细胞的形态发生明显变化,有典型神经元形态,且神经元标志物β-tubullin表达水平显著升高。说明Mash1单独作用于星形胶质细胞即可使其转变成神经元。

关键词: 神经再生, Mash-1, Brn2, β-tubullin, 重新编程, 质粒, 反转录病毒, 星形胶质细胞, 神经元, NSFC

Abstract:

To date, it remains poorly understood whether astrocytes can be easily reprogrammed into neurons. Mash1 and Brn2 have been previously shown to cooperate to reprogram fibroblasts into neurons. In this study, we examined astrocytes from 2-month-old Sprague-Dawley rats, and found that Brn2 was expressed, but Mash1 was not detectable. Thus, we hypothesized that Mash1 alone could be used to reprogram astrocytes into neurons. We transfected a recombinant MSCV-MASH1 plasmid into astrocytes for 72 hours, and saw that all cells expressed Mash1. One week later, we observed the changes in morphology of astrocytes, which showed typical neuronal characteristics. Moreover, β-tubulin expression levels were significantly higher in astrocytes expressing Mash1 than in control cells. These results indicate that Mash1 alone can reprogram astrocytes into neurons.

Key words: nerve regeneration, Mash-1, Brn2, β-tubulin, reprogram, plasmid, retrovirus, astrocytes, neurons, the National Basic Research Program of China (973 Program), neural regeneration