• 3D reconstruction and animation of the hippocampus from a GFP-M mouse.

• Ultramicroscope creates high-resolution 3D-pictures of flies

• The simulation of a scan through entire cleared brain from a GFP-M mouse

UltraMicroscope II观察内源性荧光蛋白以实现体内成像

A) 小鼠胚胎E12, 整体,三种标记;
图片由Serge van de Pavert,
VU Amsterdam提供
B) 果蝇幼虫,自发荧光;
图片由LaVision BioTec公司提供

UltraMicroscope II结合3DISCO技术用于研究小鼠神经元轴突连接

UltraMicroscopeII用于观察神经胶质瘤模型的抗体聚集

UltraMicroscope II用于研究小鼠胚胎初始淋巴管的形成机制

在哺乳动物发育过程中，主静脉血管中的内皮细胞亚群表达淋巴管特异基因，进而发育出初级的淋巴结构-淋巴囊。淋巴内皮细胞的产生经过了出芽，扩展和膨胀的过程，但是淋巴管形成的确切机制仍然不完全清楚。使用UltraMicroscope II来观察整体免疫染色的小鼠胚胎，我们以细胞水平的分辨率观察到了完整的发育中的血管系统。实验发现最早的淋巴内皮细胞宽松地连接了主静脉和浅静脉丛，进而聚集产生了两个新发现的淋巴结构，背部外周纵向淋巴管和腹侧初级胸导管，最后与主静脉相连。进一步研究其功能，发现血管内皮生长因子C和基质组分CCBE1对于淋巴内皮细胞出芽和迁移是必需的。研究使用ltraMicroscope II详细观察了淋巴管的发育并构建了新的模型。

UltraMicroscope II用于观察人类胚胎早期生长发育

UltraMicroscope II用于阐释脂肪代谢神经调控机制

部分应用文献

2) CUBIC pathology: three-dimensional imaging for pathological diagnosis. Nojima S, Susaki EA, Yoshida K, Takemoto H, Tsujimura N, Iijima S, Takachi K, Nakahara Y, Tahara S, Ohshima K, Kurashige M, Hori Y, Wada N, Ikeda JI, Kumanogoh A, Morii E, Ueda HR. Sci Rep. 2017 Aug

3) Tridimensional Visualization and Analysis of Early Human Development. Belle M, Godefroy D, Couly G, Malone SA, Collier F, Giacobini P, Chédotal A. Cell. 2017 Mar

4) Intra-islet lesions and lobular variations in β-cell mass expansion in ob/ob mice revealed by 3D imaging of intact pancreas. Parween S, Kostromina E, Nord C, Eriksson M, Lindström P, Ahlgren U. Sci Rep. 2016 Oct

5) Shrinkage-mediated imaging of entire organs and organisms using uDISCO. Pan C, Cai R, uacquarelli FP, Ghasemigharagoz A, Lourbopoulos A, Matryba P, Plesnila N, Dichgans M, Hellal F,Ertürk A. Nat Methods. 2016 Aug

6) Fully Automated Evaluation of Total Glomerular Number and Capillary Tuft Size in Nephritic Kidneys UsingLightsheet Microscopy. Klingberg A, Hasenberg A, Ludwig-Portugall I, Medyukhina A, Männ L, Brenzel A, Engel DR, Figge MT, Kurts C,Gunzer M. J Am Soc Nephrol. 2016 Aug

7) Three-Dimensional Study of Alzheimers Disease Hallmarks Using the iDISCO Clearing Method. Liebmann T, Renier N, Bettayeb K, Greengard P, Tessier-Lavigne M, Flajolet M. Cell Rep. 2016 Jul

8) Ultramicroscopy as a novel tool to unravel the tropism of AAV gene therapy vectors in the brain. Alves S, Bode J, Bemelmans AP, von Kalle C, Cartier N, Tews B. Sci Rep. 2016 Jun

9) Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes. Renier N, Adams EL, Kirst C, Wu Z, Azevedo R, Kohl J, Autry AE, Kadiri L, Umadevi Venkataraju K, Zhou Y, Wang VX, Tang CY, Olsen O, Dulac C, Osten P, Tessier-Lavigne M. Cell. 2016 Jun

10) Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences. Ye L, Allen WE, Thompson KR, Tian , Hsueh B, Ramakrishnan C, Wang AC, Jennings JH, Adhikari A, HalpernCH, Witten IB, Barth AL, Luo L, McNab JA, Deisseroth K Cell. 2016 Jun

11) Correlated magnetic resonance imaging and ultramicroscopy (MR-UM) is a tool kit to assess the dynamics of glioma angiogenesis. Breckwoldt MO, Bode J, Kurz FT, Hoffmann A, Ochs K, Ott M, Deumelandt K, Krüwel T, Schwarz D, Fischer M,Helluy X, Milford D, Kirschbaum K, Solecki G, Chiblak S, Abdollahi A, Winkler F, Wick W, Platten M, Heiland S,Bendszus M, Tews B. Elife. 2016 Feb

12) Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging. Susaki EA, Tainaka K, Perrin D, Yukinaga H, Kuno A, Ueda HR. Nat Protoc. 2015 Nov

13) Combined 3DISCO clearing method, retrograde tracer and ultramicroscopy to map corneal neurons in a whole adult mouse trigeminal ganglion. Launay PS, Godefroy D, Khabou H, Rostene W, Sahel JA, Baudouin C, Melik Parsadaniantz S, Reaux-Le Goazigo A. Exp Eye Res. 2015 Oct

14) Podoplanin and CLEC-2 drive cerebrovascular patterning and integrity during development. Lowe KL, Finney BA, Deppermann C, Hägerling R, Gazit SL, Frampton J, Buckley C, Camerer E, Nieswandt B,Kiefer F, Watson SP. Blood. 2015 Jun

15) iDISCO: A Simple, Rapid Method to Immunolabel Large Tissue Samples for Volume Imaging. Renier N, Wu Z, Simon DJ, Yang J, Ariel P, Tessier-Lavigne M. Cell. 2014 Nov

16) Whole-body imaging with single-cell resolution by tissue decolorization. Tainaka K, Kubota SI, Suyama TQ, Susaki EA, Perrin D, Ukai-Tadenuma M, Ukai H, Ueda HR. Cell. 2014 Nov

17) A Simple Method for 3D Analysis of Immunolabeled Axonal Tracts in a Transparent Nervous System. Belle M, Godefroy D, Dominici C, Heitz-Marchaland C, Zelina P, Hellal F,Bradke F, Chédotal A Cell Rep. 2014 Nov

18) Fusing VE-cadherin to α-catenin impairs fetal liver hematopoiesis and lymph but not blood vessel formation. Dartsch N, Schulte D, Hägerling R, Kiefer F, Vestweber D. Mol Cell Biol. 2014 May 9) Multispectral fluorescence ultramicroscopy: three-dimensional visualization and automatic quantification of tumor morphology, drug penetration, and antiangiogenic treatment response. Dobosz M, Ntziachristos V, Scheuer W, Strobel S Neoplasia. 2014 Jan