Chenchen Pan1,2,3, Ruiyao Cai1,2,3, Oliver Schoppe4, Ali Ertürk1,2,3*
1Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, Munich, Germany.
2Institute for Tissue Engineering and Regenerative Medicine (iTERM) Helmholtz Center Munich, Germany.
3Graduate School of Systemic Neurosciences Munich, Munich, Germany.
4Center for Translational Cancer Research (TranslaTUM) & Department of Computer Science, Germany. *Corresponding author.
The organism is a complex system composed with different organs and various types of cells. It has become more and more evident that diseases, although originally raised from restrict region, normally lead to a global impact affecting multiple parts of the body. This indicates that the organisms should be regarded as an interconnected system, both physiological and pathological alterations should be studied in an unbiased way. Recent tissue clearing methods start to play an important role in systems biology studies since it enables the screening of the transparent tissue with its entirety.
Here, we developed uDISCO and vDISCO whole-body tissue clearing methods which enables the complete scanning of adult rodent bodies with standard light-sheet microscopes. As organic solvent based tissue clearing methods. uDISCO overcomes the fast quenching of fluorescent proteins and preserves the GFP signal over month, while vDISCO achieved whole-body nanobody-based immunolabeling and imaging through the intact transparent bone and skin. By using vDISCO, we achieved the cellular level neuronal connectivity map in an entire mouse body for the first time and revealed the short connections between skull bone marrow and brain meninges as additional immune cells infiltration route. In another study, combining with a deep learning based algorithm (DeepMACT). We achieved the automated mapping of cancer metastasis and therapeutic antibody distribution at whole-body scale with cellular level resolution.
Taken together, whole-body tissue clearing methods provide a powerful platform for unbiased screening and systemic analysis of entire rodent bodies. As practical and efficient techniques, they can be readily used for various biological and biomedical researches.
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