Results
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