Journal
NATURE BIOTECHNOLOGY
Volume 37, Issue 1, Pages 73-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/nbt.4281
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Funding
- Burroughs Wellcome Fund Career Awards at the Scientific Interface
- Searle Scholars Program
- Packard Award in Science and Engineering
- NARSAD Young Investigator Award
- McKnight Foundation Technology Award
- JPB Foundation (PIIF)
- JPB Foundation (PNDRF)
- NCSOFT Cultural Foundation
- NIH [1-DP2-ES027992]
- SCSB fellowship
- Klingenstein Foundation
- Searle Scholar program (Kinship Foundation)
- Whitehall Foundation
- NIMH [R01MH107742, R01MH108594, U01MH114829]
- Anandamahidol Foundation fellowship
- NIA [P50 AG005134]
- Burroughs Wellcome Fund
- Department of Energy Computational Science Graduate Fellowship (DOE-CSGF)
- National Science Foundation [ACI-1548562]
- National Science Foundation Major Research Instrumentation program [ACI-1429830]
- HKSAR Research Grants Council (RGC) General Research Fund (GRF) [14201214]
- Chung laboratory
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [DP2ES027992] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH107742, U01MH114829, R01MH108594] Funding Source: NIH RePORTER
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Understanding complex biological systems requires the system-wide characterization of both molecular and cellular features. Existing methods for spatial mapping of biomolecules in intact tissues suffer from information loss caused by degradation and tissue damage. We report a tissue transformation strategy named stabilization under harsh conditions via intramolecular epoxide linkages to prevent degradation (SHIELD), which uses a flexible polyepoxide to form controlled intra- and intermolecular cross-link with biomolecules. SHIELD preserves protein fluorescence and antigenicity, transcripts and tissue architecture under a wide range of harsh conditions. We applied SHIELD to interrogate system-level wiring, synaptic architecture, and molecular features of virally labeled neurons and their targets in mouse at single-cell resolution. We also demonstrated rapid three-dimensional phenotyping of core needle biopsies and human brain cells. SHIELD enables rapid, multiscale, integrated molecular phenotyping of both animal and clinical tissues.
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