Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull-meninges connections

Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull-meninges connections
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DOI:
10.1038/s41593-018-0301-3
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发表时间:
2019-02-01
影响因子:
25
通讯作者:
Ertuerk, Ali
Ertuerk, Ali
中科院分区:
医学1区
文献类型:
--
作者:
Cai, Ruiyao;Pan, Chenchen;Ertuerk, Ali

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对清除后的整个透明啮齿动物身体进行分析,可以提供有关健康和疾病的整体生物学信息,但组织内部荧光蛋白信号的可靠成像和量化仍然是一个挑战。在这里,我们开发了vDISCO,这是一种压力驱动的、基于纳米体的全身免疫标记技术,可以将荧光蛋白的信号增强高达两个数量级。这使我们能够通过完整透明小鼠的骨骼、皮肤和高度自发荧光组织来成像和量化亚细胞细节。我们第一次对成年小鼠的全身神经元投射进行了可视化。我们评估了全身中枢神经系统损伤的影响,发现躯干周围神经末梢变性。此外,vDISCO发现了颅骨骨髓和脑膜之间的短血管连接,中风时脑膜充满了免疫细胞。因此,我们的新方法可以对神经系统和身体其他部分之间的相互作用进行无偏见的全面研究。
Analysis of entire transparent rodent bodies after clearing could provide holistic biological information in health and disease, but reliable imaging and quantification of fluorescent protein signals deep inside the tissues has remained a challenge. Here, we developed vDISCO, a pressure-driven, nanobody-based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image and quantify subcellular details through bones, skin and highly autofluorescent tissues of intact transparent mice. For the first time, we visualized whole-body neuronal projections in adult mice. We assessed CNS trauma effects in the whole body and found degeneration of peripheral nerve terminals in the torso. Furthermore, vDISCO revealed short vascular connections between skull marrow and brain meninges, which were filled with immune cells upon stroke. Thus, our new approach enables unbiased comprehensive studies of the interactions between the nervous system and the rest of the body.