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Protection of tissue physicochemical properties using polyfunctional crosslinkers

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 s... Full description

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 Electronic Article
Language: English
Subjects:
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.
language: eng
source:
identifier: ISSN: 1087-0156
fulltext: no_fulltext
issn:
  • 1087-0156
  • 1546-1696
url: Link


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titleProtection of tissue physicochemical properties using polyfunctional crosslinkers
creatorPark, 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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descriptionUnderstanding 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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subjectAnimal 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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descriptionUnderstanding 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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abstractUnderstanding 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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