Protection of tissue physicochemical properties using polyfunctional crosslinkers

Journal Title:	Nature biotechnology 2018-12-17, Vol.37 (1), p.73-83
Main Author:	Park, Young-Gyun
Other Authors:	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 , Kulik, Heather J , Lim, Byung Kook , Chung, Kwanghun
Format:	Electronic Article
Language:	English
Subjects:	Animal tissues Antigenicity Architecture Biomolecules Biopsy Brain Chemical properties Crosslinking Degradation Epoxy compounds Fluorescence Mapping Nucleic acids Phenotype Phenotyping Physicochemical properties Proteins Solvents Tissues Transformation Usage Wiring
Publisher:	United States: Nature Publishing Group
ID:	ISSN: 1087-0156
Link:	https://www.ncbi.nlm.nih.gov/pubmed/30556815
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title:	Protection of tissue physicochemical properties using polyfunctional crosslinkers
format:	Article
creator:	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 Kulik, Heather J Lim, Byung Kook Chung, Kwanghun
subjects:	Animal tissues Antigenicity Architecture Biomolecules Biopsy Brain Chemical properties Crosslinking Degradation Epoxy compounds Fluorescence Mapping Nucleic acids Phenotype Phenotyping Physicochemical properties Proteins Solvents Tissues Transformation Usage Wiring
ispartof:	Nature biotechnology, 2018-12-17, Vol.37 (1), p.73-83
description:	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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Protection of tissue physicochemical properties using polyfunctional crosslinkers

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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 ; Kulik, Heather J ; Lim, Byung Kook ; Chung, Kwanghun

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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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United States: Nature Publishing Group

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Animal tissues ; Antigenicity ; Architecture ; Biomolecules ; Biopsy ; Brain ; Chemical properties ; Crosslinking ; Degradation ; Epoxy compounds ; Fluorescence ; Mapping ; Nucleic acids ; Phenotype ; Phenotyping ; Physicochemical properties ; Proteins ; Solvents ; Tissues ; Transformation ; Usage ; Wiring

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Nature biotechnology, 2018-12-17, Vol.37 (1), p.73-83

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creationdate	20181217
title	Protection of tissue physicochemical properties using polyfunctional crosslinkers
author	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 ; Kulik, Heather J ; Lim, Byung Kook ; Chung, Kwanghun

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3	McCue, Margaret
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Protection of tissue physicochemical properties using polyfunctional crosslinkers

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Nature biotechnology

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Protection of tissue physicochemical properties using polyfunctional crosslinkers