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成年脊髓损伤后星形胶质细胞在体内向神经元的转化。

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

作者信息

Su Zhida, Niu Wenze, Liu Meng-Lu, Zou Yuhua, Zhang Chun-Li

机构信息

1] Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA [2] Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, 800 Xiangyin Rd, Shanghai 200433, China.

Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA.

出版信息

Nat Commun. 2014 Feb 25;5:3338. doi: 10.1038/ncomms4338.

Abstract

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.

摘要

脊髓损伤(SCI)会导致不可逆的神经元丢失和胶质瘢痕形成,最终导致持续性神经功能障碍。细胞再生可能是补充丢失细胞并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,在受伤的成年脊髓中,常驻星形胶质细胞可以通过单一转录因子SOX2转化为双皮质素(DCX)阳性神经母细胞。重要的是,这些诱导产生的神经母细胞可以在体内成熟为形成突触的神经元。组蛋白脱乙酰酶抑制剂丙戊酸(VPA)处理可进一步促进神经元成熟。本研究结果表明,将内源性星形胶质细胞原位重编程为神经元可能是SCI后细胞再生的一种潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d16/3966078/7072e972d68a/nihms561762f1.jpg

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