In vivo conversion of astrocytes to neurons in the injured adult spinal cord.

In vivo conversion of astrocytes to neurons in the injured adult spinal cord.
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DOI:
10.1038/ncomms4338
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发表时间:
2014-02-25
影响因子:
16.6
通讯作者:
Zhang, Chun-Li
Zhang, Chun-Li
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Su, Zhida;Niu, Wenze;Liu, Meng-Lu;Zou, Yuhua;Zhang, Chun-Li

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脊髓损伤(SCI)导致不可逆的神经元丢失和胶质瘢痕形成,最终导致持续的神经功能障碍。细胞再生可能是补充丢失细胞和修复损伤的理想方法。然而,成年脊髓产生新神经元的能力有限。在这里,我们表明,居民星形胶质细胞可以转换成双皮质素(DCX)阳性神经母细胞的一个单一的转录因子,SOX 2,在受伤的成年脊髓。重要的是,这些诱导的神经母细胞可以在体内成熟为突触形成神经元。用组蛋白去乙酰化酶抑制剂丙戊酸(VPA)处理可进一步促进神经元成熟。本研究的结果表明,在原位重编程的内源性星形胶质细胞的神经元可能是一个潜在的战略脊髓损伤后的细胞再生。
Spinal cord injury (SCI) leads to irreversible neuronal loss and glial scar formation, which ultimately result in persistent neurological dysfunction. Cellular regeneration could be an ideal approach to replenish the lost cells and repair the damage. However, the adult spinal cord has limited ability to produce new neurons. Here we show that resident astrocytes can be converted to doublecortin (DCX)-positive neuroblasts by a single transcription factor, SOX2, in the injured adult spinal cord. Importantly, these induced neuroblasts can mature into synapse-forming neurons in vivo. Neuronal maturation is further promoted by treatment with a histone deacetylase inhibitor, valproic acid (VPA). The results of this study indicate that in situ reprogramming of endogenous astrocytes to neurons might be a potential strategy for cellular regeneration after SCI.
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