Whole-body imaging with single-cell resolution by tissue decolorization

The development of whole-body imaging at single-cell resolution enables system-level approaches to studying cellular circuits in organisms. Previous clearing methods focused on homogenizing mismatched refractive indices of individual tissues, enabling reductions in opacity but falling short of achie...

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Veröffentlicht in:Cell 2014-11, Vol.159 (4), p.911-924
Hauptverfasser: Tainaka, Kazuki, Kubota, Shimpei I, Suyama, Takeru Q, Susaki, Etsuo A, Perrin, Dimitri, Ukai-Tadenuma, Maki, Ukai, Hideki, Ueda, Hiroki R
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container_end_page 924
container_issue 4
container_start_page 911
container_title Cell
container_volume 159
creator Tainaka, Kazuki
Kubota, Shimpei I
Suyama, Takeru Q
Susaki, Etsuo A
Perrin, Dimitri
Ukai-Tadenuma, Maki
Ukai, Hideki
Ueda, Hiroki R
description The development of whole-body imaging at single-cell resolution enables system-level approaches to studying cellular circuits in organisms. Previous clearing methods focused on homogenizing mismatched refractive indices of individual tissues, enabling reductions in opacity but falling short of achieving transparency. Here, we show that an aminoalcohol decolorizes blood by efficiently eluting the heme chromophore from hemoglobin. Direct transcardial perfusion of an aminoalcohol-containing cocktail that we previously termed CUBIC coupled with a 10 day to 2 week clearing protocol decolorized and rendered nearly transparent almost all organs of adult mice as well as the entire body of infant and adult mice. This CUBIC-perfusion protocol enables rapid whole-body and whole-organ imaging at single-cell resolution by using light-sheet fluorescent microscopy. The CUBIC protocol is also applicable to 3D pathology, anatomy, and immunohistochemistry of various organs. These results suggest that whole-body imaging of colorless tissues at high resolution will contribute to organism-level systems biology.
doi_str_mv 10.1016/j.cell.2014.10.034
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source MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; EZB-FREE-00999 freely available EZB journals
subjects Amino Alcohols - analysis
Animals
Diabetes Mellitus - pathology
Imaging, Three-Dimensional - methods
Islets of Langerhans - pathology
Male
Mice
Mice, Inbred C57BL
Single-Cell Analysis - methods
Whole Body Imaging - methods
title Whole-body imaging with single-cell resolution by tissue decolorization
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