Protection of tissue physicochemical properties using polyfunctional crosslinkers
Author(s)Park, Young-Gyun; Sohn, Chang Ho; Chen, Ritchie; McCue, Margaret Grace; Yun, Dae Hee; Drummond, Gabrielle; Ku, Taeyun; Evans, Nicholas B; Oak, Hayeon Caitlyn; Trieu, Wendy; Choi, Heejin; Jin, Xin; Lilascharoen, Varoth; Wang, Ji; Truttmann, Matthias C; Qi, Helena Wen; Ploegh, Hidde L; Golub, Todd R; Chen, Shih-Chi; Frosch, Matthew P; Kulik, Heather Janine; Lim, Byung Kook; Chung, Kwanghun; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Institute for Medical Engineering and Science; Picower Institute for Learning and Memory; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Massachusetts Institute of Technology. Department of Chemistry
Springer Science and Business Media LLC
Park, Young-Gyun et al. "Protection of tissue physicochemical properties using polyfunctional crosslinkers." Nature Biotechnology 37, 1 (January 2019): 73–83 © 2019 Nature Publishing Group
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