Structural and molecular interrogation of intact biological systems.
Structural and molecular interrogation of intact biological systems.
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从复杂的系统中获取高分辨率信息，同时维持了解系统功能所需的全球视角，这代表了生物学的关键挑战。在这里，我们使用一种方法（称为清晰度）来解决这一挑战，以将完整的组织转化为纳米多孔水凝胶杂交形式（交联至三维的亲水性聚合物网络），该网络已完全组装而成，但在光学上是透明的，且可渗透性。使用小鼠大脑，我们显示了长距离投影，局部电路接线，细胞关系，亚细胞结构，蛋白质复合物，核酸和神经递质的完整组织成像。清晰度还可以实现完整的原位杂交，免疫组织化学，在非切片组织中进行多个染色和染色，以及整个完整的成年小鼠脑中的抗体标记。最后，我们表明清晰度可以对临床样本进行精细的结构分析，包括来自神经精神疾病疾病的非剖面组织，为人类组织的传播提供了一条路径，适用于稳定，完整且可访问的形式，适合于探测结构和分子。生理功能和疾病的基础。
Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease.
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影响因子：
64.8
作者：
Bock, Davi D.;Lee, Wei-Chung Allen;Kerlin, Aaron M.;Andermann, Mark L.;Hood, Greg;Wetzel, Arthur W.;Yurgenson, Sergey;Soucy, Edward R.;Kim, Hyon Suk;Reid, R. Clay
通讯作者：
Reid, R. Clay
影响因子：
4.7
作者：
GROSSFELD, RM;SHOOTER, EM
通讯作者：
SHOOTER, EM
微光学断层扫描获得小鼠大脑的高分辨率图谱
影响因子：
56.9
作者：
Li, Anan;Gong, Hui;Luo, Qingming
通讯作者：
Luo, Qingming
影响因子：
3.2
作者：
GOLDENTHAL, KL;HEDMAN, K;WILLINGHAM, MC
通讯作者：
WILLINGHAM, MC
影响因子：
64.8
作者：
Harlow, ML;Ress, D;McMahan, UJ
通讯作者：
McMahan, UJ