NC——科学家开发中枢外细胞系删除技术 简介 在细胞上表达白喉毒素受体，可以特异性的删除某类细胞，比如在GABA能神经元上表达DTR，然后在给予DT之后就会导致该类神经元的丢失。但是最近科学家找到了一种方法，可以只删除外周的细胞系，而对中枢内的细胞系没有影响。以下是摘要： Conditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation of cells. However, diphtheria toxin (DT) crosses the blood–brain barrier, which limits its utility for ablating peripheral cells using Cre drivers that are also expressed in the central nervous system (CNS). Here we report the development of a brain-sparing DT, termed BRAINSPAReDT, for tissue-specific genetic ablation of cells outside the CNS. We prevent blood–brain barrier passage of DT through PEGylation, which polarizes the molecule and increases its size. We validate BRAINSPAReDT with regional genetic sympathectomy: BRAINSPAReDT ablates peripheral but not central catecholaminergic neurons, thus avoiding the Parkinson-like phenotype associated with full dopaminergic depletion. Regional sympathectomy compromises adipose tissue thermogenesis, and renders mice susceptible to obesity. We provide a proof of principle that BRAINSPAReDT can be used for Cre/DTR tissuespecific ablation outside the brain using CNS drivers, while consolidating the link between adiposity and the sympathetic nervous system. 1.将DT PEG化后的BRAINSPAReDT可以产生相似的细胞毒性 2.BRAINSPAReDT可以选择性删除周围神经元而对中枢无影响 3.BRAINSPAReDT可以防止PD样的运动缺陷 4.科学家选择性删除交感神经元 经典文章回顾 帕金森病患者的康复治疗 帕金森病患者的疾病预防和保健常识 10条老年性痴呆患者的护理常识 四条建议教老年人预防老年性痴呆 老年性痴呆患者的饮食禁忌和饮食调理 2016年阿尔茨海默病10大研究进展 2016年帕金森病10大研究进展 你对老年性痴呆症到底懂多少？ 地中海饮食最健康的神经科学分析 八种食物提高记忆力，增强脑活力！ 预防老年性痴呆症，先从这些小事做起！ 睡眠不足增加肥胖风险的神经科学解释 运动是大脑的最佳保健品 预防痴呆和脑中风，减少PM2.5是我们可以做的 益生菌也能够治疗痴呆、抑郁症和精神分离症？ 喜欢我，关注我 拉到最上方标题下，点击上方蓝字关注 搜索公众号名称：神经科学临床和基础 也请你推荐给你身边的医学朋友，感谢你~
Nature Chemical Biology 的一篇新论文提出了一种全新的刻画药物作用机制的方式，用RNAi技术产生一系列细胞系，用药物对这些细胞系的“response signature”来反映药物对细胞的作用特征。通过与已知药物“response signature”的相似性搜索，可以预测和鉴定新药物的作用机制（mechanism of action）。 （原文： A mammalian functional-genetic approach to characterizing cancer therapeutics ） 之前，对药物的作用机制或作用靶标的刻画主要有两类方法：一为NCI 60，一为CMAP。对这两套思路的介绍可以参考我们论文中的这段描述： "There are two methods which are commonly used to interrogate the action of compounds on cells. The first method, adopted by the Connectivity Map effort, measures a ‘compound response signature.’ In this approach gene expression signatures are established based on changes in gene expression in response to short term treatment with particular compounds; this response signature can serve as an effective tool for probing the compound(s) mechanism of action (MOA) . A second method is measurement of a ‘drug sensitivity signature’ and is used by various applications based on the National Cancer Institute NCI 60 in vitro drug screen project . The NCI 60 cell lines screen panel has proved to be an effective way to identify drug sensitivity specific biomarkers as the panel has already been comprehensively characterized via profiling at different levels (mRNA, protein, microRNAs, DNA methylation and metabolites etc.)". (全文链接： Pre-Clinical Drug Prioritization via Prognosis-Guided Genetic Interaction Networks ，PLoS ONE 2010） Nature Chemical Biology 这篇文章中的方法大致类似NCI 60的思路，不同点在于：NCI 60是利用自然发生的60中细胞系作为维度，而这篇文章是选择跟细胞生长凋亡密切相关的若干基因（针对肿瘤药物的研究），产生针对性很强的一组细胞系。 NCI 60系列与CMAP系列的最大区别在于前者内涵了表型phenotpype的信息，因此可以满足一些有针对性的任务（比如肿瘤药物筛选）。
标签: 细胞系
