title: Whole-body and Whole-Organ Clearing and Imaging Techniques with Single-Cell Resolution: Toward Organism-Level Systems Biology in Mammals.
abstract: Organism-level systems biology aims to identify, analyze, control and design cellular circuits in organisms. Many experimental and computational approaches have been developed over the years to allow us to conduct these studies. Some of the most powerful methods are based on using optical imaging in combination with fluorescent labeling, and for those one of the long-standing stumbling blocks has been tissue opacity. Recently, the solutions to this problem have started to emerge based on whole-body and whole-organ clearing techniques that employ innovative tissue-clearing chemistry. Here, we review these advancements and discuss how combining new clearing techniques with high-performing fluorescent proteins or small molecule tags, rapid volume imaging and efficient image informatics is resulting in comprehensive and quantitative organ-wide, single-cell resolution experimental data. These technologies are starting to yield information on connectivity and dynamics in cellular circuits at unprecedented resolution, and bring us closer to system-level understanding of physiology and diseases of complex mammalian systems.
authors.affiliation: Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan; Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center (QBiC), 1-3, Yamadaoka, Suita, Osaka 565-0874, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), 1-7-1, Ohte-machi, Chiyoda-ku, Tokyo, 100-0004, Japan.
authors.forename: Etsuo A
authors.initials: EA
authors.lastname: Susaki
authors.affiliation: Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center (QBiC), 1-3, Yamadaoka, Suita, Osaka 565-0874, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), 1-7-1, Ohte-machi, Chiyoda-ku, Tokyo, 100-0004, Japan. Electronic address: uedah-tky@umin.ac.jp.
authors.forename: Hiroki R
authors.initials: HR
authors.lastname: Ueda
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D001931:Brain Mapping / Q000379:methods*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D008853:Microscopy / Q000379:methods; D061848:Optical Imaging / Q000379:methods*; D059010:Single-Cell Analysis / Q000379:methods*; D049490:Systems Biology / Q000379:methods*; D051598:Whole Body Imaging / Q000379:methods*