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Nat Methods. 2016 Oct;13(10):859-67. doi: 10.1038/nmeth.3964. Epub 2016 Aug 22.

Shrinkage-mediated imaging of entire organs and organisms using uDISCO.

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Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilians University of Munich (LMU), Munich, Germany.
Graduate School of Systemic Neurosciences (GSN), Munich, Germany.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.


Recent tissue-clearing approaches have become important alternatives to standard histology approaches. However, light scattering in thick tissues and the size restrictions on samples that can be imaged with standard light-sheet microscopy pose limitations for analyzing large samples such as an entire rodent body. We developed 'ultimate DISCO' (uDISCO) clearing to overcome these limitations in volumetric imaging. uDISCO preserves fluorescent proteins over months and renders intact organs and rodent bodies transparent while reducing their size up to 65%. We used uDISCO to image neuronal connections and vasculature from head to toe over 7 cm and to perform unbiased screening of transplanted stem cells within the entire body of adult mice. uDISCO is compatible with diverse labeling methods and archival human tissue, and it can readily be used in various biomedical applications to study organization of large organ systems throughout entire organisms.

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