小柯机器人

美国斯克里普斯研究所Li Ye课题组开发出用于透明化哺乳动物身体的新方法。这一研究成果于2022年3月28日在线发表在国际学术期刊《自然—方法学》上。

研究人员开发了HYBRiD（基于水凝胶的强化三维成像的溶剂透明器官（DISCO）），通过重新组合基于有机物和聚合物的清除管道的组件。在透明的哺乳动物体内，研究人员实现了高透明度和蛋白质保留，以及与直接荧光成像和免疫染色的兼容性。利用小清蛋白-Cre和生长抑素-Cre模型，研究人员证明了HYBRiD在新生小鼠和幼年小鼠中对基因编码的荧光报告器进行全身成像的效用，而没有依赖抗体对信号的增强。

使用K18-hACE2转基因小鼠，HYBRiD使SARS-CoV-2感染在整个小鼠胸部的无灌注清除和可视化，揭示了同一样本中病毒病理学的宏观和微观特征。HYBRiD为基础和转化研究提供了一个简单和通用的解决方案，使大型异质身体部位或整个动物可视化。

据介绍，最近，基于溶剂和聚合物的脑透明技术的发展提高了人们对哺乳动物神经系统进行三维可视化的能力。然而，对哺乳动物身体进行整体成像仍然是一个挑战。

附：英文原文

Title: HYBRiD: hydrogel-reinforced DISCO for clearing mammalian bodies

Author: Nudell, Victoria, Wang, Yu, Pang, Zhengyuan, Lal, Neeraj K., Huang, Min, Shaabani, Namir, Kanim, Wesam, Teijaro, John, Maximov, Anton, Ye, Li

Issue&Volume: 2022-03-28

Abstract: The recent development of solvent- and polymer-based brain-clearing techniques has advanced our ability to visualize the mammalian nervous system in three dimensions. However, it remains challenging to image the mammalian body en bloc. Here we developed HYBRiD (hydrogel-based reinforcement of three-dimensional imaging solvent-cleared organs (DISCO)), by recombining components of organic- and polymer-based clearing pipelines. We achieved high transparency and protein retention, as well as compatibility with direct fluorescent imaging and immunostaining in cleared mammalian bodies. Using parvalbumin- and somatostatin-Cre models, we demonstrated the utility of HYBRiD for whole-body imaging of genetically encoded fluorescent reporters without antibody enhancement of signals in newborn and juvenile mice. Using K18-hACE2 transgenic mice, HYBRiD enabled perfusion-free clearing and visualization of SARS-CoV-2 infection in a whole mouse chest, revealing macroscopic and microscopic features of viral pathology in the same sample. HYBRiD offers a simple and universal solution to visualize large heterogeneous body parts or entire animals for basic and translational research. HYBRiD is a tissue-clearing approach that combines elements of solvent-based and aqueous, hydrogel-based methods, thereby achieving high transparency while maintaining fluorescence.

DOI: 10.1038/s41592-022-01427-0

Source: https://www.nature.com/articles/s41592-022-01427-0

Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex