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Title: Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues
Authors: Susaki, Etsuo A.
Shimizu, Chika
Kuno, Akihiro
Tainaka, Kazuki
Li, Xiang
Nishi, Kengo
Morishima, Ken  kyouindb  KAKEN_id  orcid (unconfirmed)
Ono, Hiroaki
Ode, Koji L.
Saeki, Yuki
Miyamichi, Kazunari
Isa, Kaoru
Yokoyama, Chihiro
Kitaura, Hiroki
Ikemura, Masako
Ushiku, Tetsuo
Shimizu, Yoshihiro
Saito, Takashi
Saido, Takaomi C.
Fukayama, Masashi
Onoe, Hirotaka
Touhara, Kazushige
Isa, Tadashi  kyouindb  KAKEN_id
Kakita, Akiyoshi
Shibayama, Mitsuhiro
Ueda, Hiroki R.
Author's alias: 伊佐, 正
Issue Date: Dec-2020
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 11
Abstract: Whole-organ/body three-dimensional (3D) staining and imaging have been enduring challenges in histology. By dissecting the complex physicochemical environment of the staining system, we developed a highly optimized 3D staining imaging pipeline based on CUBIC. Based on our precise characterization of biological tissues as an electrolyte gel, we experimentally evaluated broad 3D staining conditions by using an artificial tissue-mimicking material. The combination of optimized conditions allows a bottom-up design of a superior 3D staining protocol that can uniformly label whole adult mouse brains, an adult marmoset brain hemisphere, an ~1 cm3 tissue block of a postmortem adult human cerebellum, and an entire infant marmoset body with dozens of antibodies and cell-impermeant nuclear stains. The whole-organ 3D images collected by light-sheet microscopy are used for computational analyses and whole-organ comparison analysis between species. This pipeline, named CUBIC-HistoVIsion, thus offers advanced opportunities for organ- and organism-scale histological analysis of multicellular systems.
Rights: © The Author(s) 2020 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI(Published Version): 10.1038/s41467-020-15906-5
PubMed ID: 32341345
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