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科学家对不同中间神经元进行病毒操作
作者:小柯机器人 发布时间:2020/8/18 16:33:48

美国哈佛和麻省理工学院Jordane Dimidschstein课题组近日取得一项新成果。他们对小鼠、非人类灵长类动物和人类中功能不同的中间神经元进行病毒操作。相关论文发表在2020年8月17日出版的《自然-神经科学》杂志上。

他们开发了一种策略,该策略可鉴定出多种新的增强子以靶向功能不同的神经元亚型。通过研究疾病基因Scn1a的调控图谱,他们发现了能够选择小白蛋白(PV)和表达血管活性肠肽中间神经元的增强子。通过展示这些元件的功能用途,他们表明PV特异性增强子可跨脊椎动物物种(包括人类)选择性地靶向和操纵这些神经元。

最后,他们证明了他们的选择方法是可推广的,并且可以表征在不同大脑区域内具有特殊特异性的其他PV特异性增强子。总之,这些病毒工具可用于特定细胞类型的环路操纵,并有望用于治疗性干预。这项研究描述了一系列新的基因调控序列,这些序列将病毒转基因的表达限制到特定的中间神经元亚型,从而可以选择性地监测和操纵它们从小鼠到人类的活性。

据悉,在重组腺相关病毒载体的背景下鉴定基因调控元件的最新研究,使细胞类型限制的基因表达成为可能。但是,在大脑皮层中,这些工具在很大程度上限于广泛的神经元类别。

附:英文原文

Title: Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans

Author: Douglas Vormstein-Schneider, Jessica D. Lin, Kenneth A. Pelkey, Ramesh Chittajallu, Baolin Guo, Mario A. Arias-Garcia, Kathryn Allaway, Sofia Sakopoulos, Gates Schneider, Olivia Stevenson, Josselyn Vergara, Jitendra Sharma, Qiangge Zhang, Tom P. Franken, Jared Smith, Leena A. Ibrahim, Kevin J. M astro, Ehsan Sabri, Shuhan Huang, Emilia Favuzzi, Timothy Burbridge, Qing Xu, Lihua Guo, Ian Vogel, Vanessa Sanchez, Giuseppe A. Saldi, Bram L. Gorissen, Xiaoqing Yuan, Kareem A. Zaghloul, Orrin Devinsky, Bernardo L. Sabatini, Renata Batista-Brito, John Reynolds, Guoping Feng, Zhanyan Fu, Chris J. McBain, Gord Fishell, Jordane Dimidschstein

Issue&Volume: 2020-08-17

Abstract: Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we discovered enhancers selective for parvalbumin (PV) and vasoactive intestinal peptide-expressing interneurons. Demonstrating the functional utility of these elements, we show that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across vertebrate species, including humans. Finally, we demonstrate that our selection method is generalizable and characterizes additional PV-specific enhancers with exquisite specificity within distinct brain regions. Altogether, these viral tools can be used for cell-type-specific circuit manipulation and hold considerable promise for use in therapeutic interventions. This study describes a series of new gene-regulatory sequences that restrict expression of viral transgenes to specific interneuron subtypes, allowing for selective monitoring and manipulation of their activity from mice to humans.

DOI: 10.1038/s41593-020-0692-9

Source: https://www.nature.com/articles/s41593-020-0692-9

期刊信息

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新if:21.126
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex