Journal
NATURE
Volume 497, Issue 7449, Pages 332-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature12107
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Funding
- National Institutes of Health (NIH) from NIMH [TR01]
- NSF
- Simons Foundation
- Stanford University
- NIDA
- DARPA REPAIR program
- Wiegers Foundation
- Snyder Foundation
- Reeves Foundation
- Gatsby Foundation
- Yu Foundation
- Burroughs Wellcome Fund Career Award at the Scientific Interface
- Samsung Scholarship
- Helen Hay Whitney Foundation
- NSF Graduate Research Fellowship
- NIH MSTP
- Deisseroth laboratory
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [1247950] Funding Source: National Science Foundation
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Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease.
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