中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (8): 828-836.doi: 10.4103/1673-5374.131599

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

miR-21如何促进毛囊神经嵴干细胞向许旺细胞分化?

  

  • 收稿日期:2014-03-08 出版日期:2014-04-25 发布日期:2014-04-25
  • 基金资助:

    国家自然科学基金项目(81070855)

miR-21 promotes the differentiation of hair follicle-derived neural crest stem cells into Schwann cells

Yuxin Ni1, Kaizhi Zhang2, Xuejuan Liu3, Tingting Yang 1, Baixiang Wang 1, Li Fu 1, Lan A 1, Yanmin Zhou 1   

  1. 1 Hospital of Stomatology, Jilin University, Changchun, Jilin Province, China
    2 China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China
    3 First Hospital of Jilin University, Changchun, Jilin Province, China
  • Received:2014-03-08 Online:2014-04-25 Published:2014-04-25
  • Contact: Yanmin Zhou, Ph.D., M.D., Hospital of Stomatology, Jilin University, Changchun 130021, Jilin Province, China, neurology@live.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81070855.

摘要:

毛囊神经嵴干细胞在体内外实验中均可分化为许旺细胞,但分化过程中的调节机制目前尚未完全清楚。实验从人毛囊中分离神经嵴干细胞转染miR-21后,定向诱导为许旺细胞。定量RT-PCR检测发现,miR-21在神经嵴干细胞分化为许旺细胞的过程中表达逐渐升高。转染miR-21激动剂agomir-21后,干细胞分化为许旺细胞的能力增强,而转染miR-21的抑制剂antagomir-21后,干细胞的分化能力则减弱。进一步研究发现,SOX2是miR-21的作用靶点,miR-21可在不影响SOX2 mRNA水平的情况下通过与其3’-UTR段结合而下调SOX蛋白表达。结果证实,在神经嵴干细胞中敲除SOX2基因可显著逆转antagomir-21抑制干细胞分化为许旺细胞的能力,说明miR-21可通过与SOX2 mRNA 3’-UTR段结合下调其蛋白表达,从而促进神经嵴干细胞向许旺细胞分化,发挥修复周围神经损伤的作用。

Abstract:

Hair follicle-derived neural crest stem cells can be induced to differentiate into Schwann cells in vivo and in vitro. However, the underlying regulatory mechanism during cell differentiation remains poorly understood. This study isolated neural crest stem cells from human hair follicles and induced them to differentiate into Schwann cells. Quantitative RT-PCR showed that microRNA (miR)-21 expression was gradually increased during the differentiation of neural crest stem cells into Schwann cells. After transfection with the miR-21 agonist (agomir-21), the differentiation capacity of neural crest stem cells was enhanced. By contrast, after transfection with the miR-21 antagonist (antagomir-21), the differentiation capacity was attenuated. Further study results showed that SOX-2 was an effective target of miR-21. Without compromising SOX2 mRNA expression, miR-21 can down-regulate SOX protein expression by binding to the 3′-UTR of miR-21 mRNA. Knocking out the SOX2 gene from the neural crest stem cells significantly reversed the antagomir-21 inhibition of neural crest stem cells differentiating into Schwann cells. The results suggest that miR-21 expression was increased during the differentiation of neural crest stem cells into Schwann cells and miR-21 promoted the differentiation through down-regulating SOX protein expression by binding to the 3′-UTR of SOX2 mRNA.

Key words: nerve regeneration, microRNA, stem cells, Schwann cells, SOX2, hair follicle, neural crest stem cells, neurons, NSFC grant, neural regeneration