当前位置:科学网首页 > 小柯机器人 >详情
线粒体蛋白影响胶质细胞命运转换
作者:小柯机器人 发布时间:2020/11/17 16:12:42

德国路德维希-马克西米利安斯大学(LMU)Magdalena Gtz团队取得最新进展。他们发现CRISPR介导的富含神经元线粒体蛋白的诱导促进直接胶质细胞向神经元的转化。该项研究成果发表在2020年11月16日的《细胞-干细胞》上。

他们确定了皮质星形胶质细胞和神经元的全面线粒体蛋白质组,确定了每种细胞类型(包括转运蛋白、代谢酶和特定于细胞类型的抗氧化剂)中约150种明显富集的线粒体蛋白质。在重编程过程中监视它们的转运,揭示了晚期和仅部分适应神经元身份。早期dCas9介导的编码线粒体蛋白基因的激活显著提高转化效率,特别是对于富含神经元但不富含星形胶质细胞的抗氧化剂蛋白。

例如,Sod1不仅提高了转化神经元的存活率,而且引发了更快的转化速度,表明线粒体蛋白在此过程中起着促进剂和驱动器的作用。具有其他功能的线粒体蛋白质的转录工程也改善了重编程,证明了线粒体蛋白质在命运转换过程中的作用更为广泛。

研究人员表示,星形胶质细胞向神经元的转化是神经元替代疗法的潜在途径。神经元特别依赖于线粒体功能,但是线粒体如何适应新的命运尚不清楚。

附:英文原文

Title: CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion

Author: Gianluca L. Russo, Giovanna Sonsalla, Poornemaa Natarajan, Christopher T. Breunig, Giorgia Bulli, Juliane Merl-Pham, Sabine Schmitt, Jessica Giehrl-Schwab, Florian Giesert, Martin Jastroch, Hans Zischka, Wolfgang Wurst, Stefan H. Stricker, Stefanie M. Hauck, Giacomo Masserdotti, Magdalena Gtz

Issue&Volume: 2020-11-16

Abstract: Astrocyte-to-neuron conversion is a promising avenue for neuronal replacement therapy. Neurons are particularly dependent on mitochondrial function, but how well mitochondria adapt to the new fate is unknown. Here, we determined the comprehensive mitochondrial proteome of cortical astrocytes and neurons, identifying about 150 significantly enriched mitochondrial proteins for each cell type, including transporters, metabolic enzymes, and cell-type-specific antioxidants. Monitoring their transition during reprogramming revealed late and only partial adaptation to the neuronal identity. Early dCas9-mediated activation of genes encoding mitochondrial proteins significantly improved conversion efficiency, particularly for neuron-enriched but not astrocyte-enriched antioxidant proteins. For example, Sod1 not only improves the survival of the converted neurons but also elicits a faster conversion pace, indicating that mitochondrial proteins act as enablers and drivers in this process. Transcriptional engineering of mitochondrial proteins with other functions improved reprogramming as well, demonstrating a broader role of mitochondrial proteins during fate conversion.

DOI: 10.1016/j.stem.2020.10.015

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30509-9

 

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx