Protection of tissue physicochemical properties using polyfunctional crosslinkers

Young Gyun Park; Chang Ho Sohn; Ritchie Chen; Margaret McCue; Dae Hee Yun; Gabrielle T. Drummond; Taeyun Ku; Nicholas B. Evans; Hayeon Caitlyn Oak; Wendy Trieu; Heejin Choi; Xin Jin; Varoth Lilascharoen; Ji Wang; Matthias C. Truttmann; Helena W. Qi; Hidde L. Ploegh; Todd R. Golub; Shih Chi Chen; Matthew P. Frosch; Heather J. Kulik; Byung Kook Lim; Kwanghun Chung

doi:10.1038/nbt.4281

Protection of tissue physicochemical properties using polyfunctional crosslinkers

Young Gyun Park, Chang Ho Sohn, Ritchie Chen, Margaret McCue, Dae Hee Yun, Gabrielle T. Drummond, Taeyun Ku, Nicholas B. Evans, Hayeon Caitlyn Oak, Wendy Trieu, Heejin Choi, Xin Jin, Varoth Lilascharoen, Ji Wang, Matthias C. Truttmann, Helena W. Qi, Hidde L. Ploegh, Todd R. Golub, Shih Chi Chen, Matthew P. FroschHeather J. Kulik, Byung Kook Lim, Kwanghun Chung

Yonsei Advanced Science Institute

Research output: Contribution to journal › Article › peer-review

144 Citations (Scopus)

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.

Original language	English
Pages (from-to)	73
Number of pages	1
Journal	Nature Biotechnology
Volume	37
Issue number	1
DOIs	https://doi.org/10.1038/nbt.4281
Publication status	Published - 2019 Jan 1

Bibliographical note

Funding Information:
The authors thank the entire Chung laboratory for support and discussions. We acknowledge S. Speck, A. Tran, J. Senecal, W. Guan and L. Kamentsky for their contribution to image processing and data analysis. K.C. was supported by the Burroughs Wellcome Fund Career Awards at the Scientific Interface, Searle Scholars Program, Packard Award in Science and Engineering, NARSAD Young Investigator Award, McKnight Foundation Technology Award, JPB Foundation (PIIF and PNDRF), NCSOFT Cultural Foundation and NIH (1-DP2-ES027992). R.C. was supported by a SCSB fellowship. B.K.L. was supported by the Klingenstein Foundation, Searle Scholar program (Kinship Foundation), Whitehall Foundation, NARSAD Young Investigator Award and grants from NIMH (R01MH107742, R01MH108594, U01MH114829). V.L. is supported by Anandamahidol Foundation fellowship. M.P.F. was partially supported by NIA P50 AG005134. H.J.K. holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund, which supported the work. H.W.Q. was supported in part by a Department of Energy Computational Science Graduate Fellowship (DOE-CSGF). This work was carried out in part using computational resources from the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant ACI-1548562. This work used the XStream computational resource, supported by the National Science Foundation Major Research Instrumentation program (ACI-1429830). S.-C.C. and J.W. were supported by HKSAR Research Grants Council (RGC) General Research Fund (GRF), number 14201214. K.C. is a cofounder of LifeCanvas Technologies, a startup that aims to help the research community adopt technologies developed by the Chung Laboratory.

Publisher Copyright:
© 2019, Nature Publishing Group. All rights reserved.

All Science Journal Classification (ASJC) codes

Applied Microbiology and Biotechnology
Bioengineering
Molecular Medicine
Biotechnology
Biomedical Engineering

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Park, Y. G., Sohn, C. H., Chen, R., McCue, M., Yun, D. H., Drummond, G. T., Ku, T., Evans, N. B., Oak, H. C., Trieu, W., Choi, H., Jin, X., Lilascharoen, V., Wang, J., Truttmann, M. C., Qi, H. W., Ploegh, H. L., Golub, T. R., Chen, S. C., ... Chung, K. (2019). Protection of tissue physicochemical properties using polyfunctional crosslinkers. Nature Biotechnology, 37(1), 73. https://doi.org/10.1038/nbt.4281

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title = "Protection of tissue physicochemical properties using polyfunctional crosslinkers",

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.",

author = "Park, {Young Gyun} and Sohn, {Chang Ho} and Ritchie Chen and Margaret McCue and Yun, {Dae Hee} and Drummond, {Gabrielle T.} and Taeyun Ku and Evans, {Nicholas B.} and Oak, {Hayeon Caitlyn} and Wendy Trieu and Heejin Choi and Xin Jin and Varoth Lilascharoen and Ji Wang and Truttmann, {Matthias C.} and Qi, {Helena W.} and Ploegh, {Hidde L.} and Golub, {Todd R.} and Chen, {Shih Chi} and Frosch, {Matthew P.} and Kulik, {Heather J.} and Lim, {Byung Kook} and Kwanghun Chung",

note = "Funding Information: The authors thank the entire Chung laboratory for support and discussions. We acknowledge S. Speck, A. Tran, J. Senecal, W. Guan and L. Kamentsky for their contribution to image processing and data analysis. K.C. was supported by the Burroughs Wellcome Fund Career Awards at the Scientific Interface, Searle Scholars Program, Packard Award in Science and Engineering, NARSAD Young Investigator Award, McKnight Foundation Technology Award, JPB Foundation (PIIF and PNDRF), NCSOFT Cultural Foundation and NIH (1-DP2-ES027992). R.C. was supported by a SCSB fellowship. B.K.L. was supported by the Klingenstein Foundation, Searle Scholar program (Kinship Foundation), Whitehall Foundation, NARSAD Young Investigator Award and grants from NIMH (R01MH107742, R01MH108594, U01MH114829). V.L. is supported by Anandamahidol Foundation fellowship. M.P.F. was partially supported by NIA P50 AG005134. H.J.K. holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund, which supported the work. H.W.Q. was supported in part by a Department of Energy Computational Science Graduate Fellowship (DOE-CSGF). This work was carried out in part using computational resources from the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant ACI-1548562. This work used the XStream computational resource, supported by the National Science Foundation Major Research Instrumentation program (ACI-1429830). S.-C.C. and J.W. were supported by HKSAR Research Grants Council (RGC) General Research Fund (GRF), number 14201214. K.C. is a cofounder of LifeCanvas Technologies, a startup that aims to help the research community adopt technologies developed by the Chung Laboratory. Publisher Copyright: {\textcopyright} 2019, Nature Publishing Group. All rights reserved.",

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Park, YG, Sohn, CH, Chen, R, McCue, M, Yun, DH, Drummond, GT, Ku, T, Evans, NB, Oak, HC, Trieu, W, Choi, H, Jin, X, Lilascharoen, V, Wang, J, Truttmann, MC, Qi, HW, Ploegh, HL, Golub, TR, Chen, SC, Frosch, MP, Kulik, HJ, Lim, BK & Chung, K 2019, 'Protection of tissue physicochemical properties using polyfunctional crosslinkers', Nature Biotechnology, vol. 37, no. 1, pp. 73. https://doi.org/10.1038/nbt.4281

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AU - Ku, Taeyun

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AU - Oak, Hayeon Caitlyn

AU - Trieu, Wendy

AU - Choi, Heejin

AU - Jin, Xin

AU - Lilascharoen, Varoth

AU - Wang, Ji

AU - Truttmann, Matthias C.

AU - Qi, Helena W.

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N2 - 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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Bibliographical note

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