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Mai, H. ; Luo ; Höher, L. ; Al-Maskari, R. ; Horvath, I. ; Chen, Y. ; Kofler, F. ; Piraud, M. ; Paetzold, J.C. ; Modamio Chamarro, J. ; Todorov, M.I. ; Elsner, M. ; Hellal, F. ; Ertürk, A.

Whole-body cellular mapping in mouse using standard IgG antibodies.

Nat. Biotechnol., DOI: 10.1038/s41587-023-01846-0 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Whole-body imaging techniques play a vital role in exploring the interplay of physiological systems in maintaining health and driving disease. We introduce wildDISCO, a new approach for whole-body immunolabeling, optical clearing and imaging in mice, circumventing the need for transgenic reporter animals or nanobody labeling and so overcoming existing technical limitations. We identified heptakis(2,6-di-O-methyl)-β-cyclodextrin as a potent enhancer of cholesterol extraction and membrane permeabilization, enabling deep, homogeneous penetration of standard antibodies without aggregation. WildDISCO facilitates imaging of peripheral nervous systems, lymphatic vessels and immune cells in whole mice at cellular resolution by labeling diverse endogenous proteins. Additionally, we examined rare proliferating cells and the effects of biological perturbations, as demonstrated in germ-free mice. We applied wildDISCO to map tertiary lymphoid structures in the context of breast cancer, considering both primary tumor and metastases throughout the mouse body. An atlas of high-resolution images showcasing mouse nervous, lymphatic and vascular systems is accessible at http://discotechnologies.org/wildDISCO/atlas/index.php .
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Intact; Tissue; Organs; Cells
ISSN (print) / ISBN 1087-0156
e-ISSN 1546-1696
Journal Nature Biotechnology
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Tissue Engineering and Regenerative Medicine (ITERM)
Helmholtz Artifical Intelligence Cooperation Unit (HAICU)
Grants
Nomis Heart Atlas Project Grant (Nomis Foundation)
European Research Council Consolidator grant
German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung, BMBF) within the NATON collaboration
DFG
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy
Vascular Dementia Research Foundation
China Scholarship Council