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miR-9 在小鼠视网膜干细胞神经元分化中的作用。

The role of miR-9 during neuron differentiation of mouse retinal stem cells.

机构信息

a Department of Ophthalmology, Beijing Chaoyang Hospital , Capital Medical University , Beijing , P.R. China.

出版信息

Artif Cells Nanomed Biotechnol. 2016 Dec;44(8):1883-1890. doi: 10.3109/21691401.2015.1111231. Epub 2015 Dec 24.

Abstract

Retinal stem cells (RSCs) have been defined as neural cells with the potential to self-renew and to generate all the different cell types of the nervous system following differentiation, which are an ideal engraft in retinal regeneration. In this research, mouse RSCs were isolated from retina, induced differentiation into neuron cells in vitro after over-expression of miR-9. The results showed that the RSCs could induce differentiation into neuron cells under the special medium, but when the miR-9 was over-expressed, the differentiated efficiency of neuron cells from RSCs could be promoted. This reason was demonstrated that polypyrimidine tract-binding protein 1 (PTBP1) was a repressor for polypyrimidine tract-binding protein 2 (PTBP2), during neuronal differentiation, miR-9 reduced PTBP1 levels, leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. And then miR-9 promoted neuron cells from RSCs were successful colonized into injured spinal cord for participation in tissue-repair. In conclusion, our research showed that the miR-9 promoted the differentiation of neuronal cells from RSCs, and this mechanism was miR-9 reduced the expression of PTBP1, increased the expression of PTBP2.

摘要

视网膜干细胞 (RSCs) 被定义为具有自我更新能力的神经细胞,能够在分化后产生神经系统的所有不同细胞类型,是视网膜再生的理想移植细胞。在这项研究中,我们从老鼠的视网膜中分离出 RSCs,在过表达 miR-9 后,将其在体外诱导分化为神经元细胞。结果表明,在特殊培养基中,RSCs 可以诱导分化为神经元细胞,但当 miR-9 过表达时,RSCs 分化为神经元细胞的效率可以得到促进。原因是多嘧啶 tract-binding 蛋白 1 (PTBP1) 是多嘧啶 tract-binding 蛋白 2 (PTBP2) 的抑制剂,在神经元分化过程中,miR-9 降低了 PTBP1 的水平,导致正确剪接的 PTBP2 mRNA 积累,并显著增加了 PTBP2 蛋白的水平。然后,miR-9 促进了 RSCs 中的神经元细胞成功定植到受损的脊髓中,参与组织修复。总之,我们的研究表明,miR-9 促进了 RSCs 中神经元细胞的分化,这种机制是 miR-9 降低了 PTBP1 的表达,增加了 PTBP2 的表达。

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