4.4 Review

Tissue clearing and its applications in neuroscience

Journal

NATURE REVIEWS NEUROSCIENCE
Volume 21, Issue 2, Pages 61-79

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41583-019-0250-1

Keywords

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Funding

  1. Brain/MINDS
  2. Basic Science and Platform Technology Program for Innovative Biological Medicine (AMED/MEXT)
  3. Japan Society for the Promotion of Science
  4. Human Frontier Science Program Research Grant Program [HFSP RGP0019/2018]
  5. Munich Cluster for Systems Neurology (SyNergy)
  6. Fritz Thyssen Stiftung
  7. Deutsche Forschungsgemeinschaft
  8. David and Lucile Packard Foundation (Packard Fellowship)
  9. McKnight Foundation
  10. US National Institutes of Health (NIH) [1-DP2-ES027992, U01MH117072]
  11. NCSOFT Cultural Foundation
  12. Koreaan Institute for Basic Science [IBS-R026-D1]
  13. NIH BRAIN Initiative
  14. NIH Office of the Director
  15. US National Science Foundation (NeuroNex)
  16. LABEX LIFESENSES [ANR-10-LABX-65, ANR-11-IDEX-0004-02]
  17. European Regional Development Fund of the Czech IT4Innovations National Supercomputing Center within the Czech Research, Development and Education Operational Programme [CZ.02.1.01/0.0/0.0/16_013/0001791]
  18. Howard Hughes Medical Institute

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State-of-the-art tissue-clearing methods provide subcellular-level optical access to intact tissues from individual organs and even to some entire mammals. When combined with light-sheet microscopy and automated approaches to image analysis, existing tissue-clearing methods can speed up and may reduce the cost of conventional histology by several orders of magnitude. In addition, tissue-clearing chemistry allows whole-organ antibody labelling, which can be applied even to thick human tissues. By combining the most powerful labelling, clearing, imaging and data-analysis tools, scientists are extracting structural and functional cellular and subcellular information on complex mammalian bodies and large human specimens at an accelerated pace. The rapid generation of terabyte-scale imaging data furthermore creates a high demand for efficient computational approaches that tackle challenges in large-scale data analysis and management. In this Review, we discuss how tissue-clearing methods could provide an unbiased, system-level view of mammalian bodies and human specimens and discuss future opportunities for the use of these methods in human neuroscience. Tissue-clearing methods are now allowing 3D imaging of intact tissues and some entire mammals. In this Review, Ueda and colleagues discuss the various tissue-clearing methods, related techniques and data analysis and management, as well as the application of these methods in neuroscience.

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