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突触囊泡蛋白2A(SV2A)的缺失通过p53信号通路促进人神经干细胞凋亡。

Loss of SV2A promotes human neural stem cell apoptosis via p53 signaling.

作者信息

Yu Hongxiang, Han Yingying, Cui Can, Li Gang, Zhang Bei

机构信息

Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China.

Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China.

出版信息

Neurosci Lett. 2023 Mar 13;800:137125. doi: 10.1016/j.neulet.2023.137125. Epub 2023 Feb 11.

Abstract

This study investigated the role of synaptic vesicle protein 2A (SV2A) in the regulation of human induced pluripotent stem cell-derived neural stem cells (NSCs). SV2A was highly expressed in NSCs. SV2A knockdown promotes apoptosis, which was associated with an upregulation of genes involved in p53 signaling as determined by transcriptome analysis. Treatment with the small molecule p53 inhibitor pifithrin-α reversed the promotion of NSC apoptosis induced by loss of SV2A. These results demonstrate that SV2A plays an important role in regulating NSC survival via the p53 signaling pathway.

摘要

本研究调查了突触小泡蛋白2A(SV2A)在调控人诱导多能干细胞衍生的神经干细胞(NSCs)中的作用。SV2A在神经干细胞中高表达。通过转录组分析确定,SV2A基因敲低可促进细胞凋亡,这与p53信号通路相关基因的上调有关。用小分子p53抑制剂pifithrin-α处理可逆转因SV2A缺失诱导的神经干细胞凋亡的促进作用。这些结果表明,SV2A通过p53信号通路在调节神经干细胞存活中起重要作用。

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