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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2020
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| Online Access: | https://hdl.handle.net/1721.1/128842 |
| _version_ | 1826189529984270336 |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science 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 |
| author_sort | Park, Young-Gyun |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T08:16:18Z |
| format | Article |
| id | mit-1721.1/128842 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:16:18Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1288422022-09-23T12:03:16Z Protection of tissue physicochemical properties using polyfunctional crosslinkers 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 Massachusetts Institute of Technology. Institute for Medical Engineering & 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 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. NIH (Grant 1-DP2-ES027992) NIMH (Grants R01MH107742, R01MH108594, U01MH114829) 2020-12-16T16:00:54Z 2020-12-16T16:00:54Z 2018-12 2018-03 2019-08-16T13:24:10Z Article http://purl.org/eprint/type/JournalArticle 1087-0156 1546-1696 https://hdl.handle.net/1721.1/128842 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 en http://dx.doi.org/10.1038/nbt.4281 Nature Biotechnology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | 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 Protection of tissue physicochemical properties using polyfunctional crosslinkers |
| title | Protection of tissue physicochemical properties using polyfunctional crosslinkers |
| title_full | Protection of tissue physicochemical properties using polyfunctional crosslinkers |
| title_fullStr | Protection of tissue physicochemical properties using polyfunctional crosslinkers |
| title_full_unstemmed | Protection of tissue physicochemical properties using polyfunctional crosslinkers |
| title_short | Protection of tissue physicochemical properties using polyfunctional crosslinkers |
| title_sort | protection of tissue physicochemical properties using polyfunctional crosslinkers |
| url | https://hdl.handle.net/1721.1/128842 |
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