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- Title
Protection of tissue physicochemical properties using polyfunctional crosslinkers.
- Authors
Park, Young-Gyun; Sohn, Chang Ho; Chen, Ritchie; McCue, Margaret; Yun, Dae Hee; Drummond, Gabrielle T; Ku, Taeyun; Evans, Nicholas B; Oak, Hayeon Caitlyn; Trieu, Wendy; Choi, Heejin; Jin, Xin; Lilascharoen, Varoth; Wang, Ji; Truttmann, Matthias C; Qi, Helena W; Ploegh, Hidde L; Golub, Todd R; Chen, Shih-Chi; Frosch, Matthew P
- Abstract
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.
- Publication
Nature Biotechnology, 2019, Vol 37, Issue 1, p73
- ISSN
1087-0156
- Publication type
Academic Journal
- DOI
10.1038/nbt.4281