Protection of tissue physicochemical properties using polyfunctional crosslinkers

被引：258

作者：

Park, Young-Gyun ^{[1
,2
]}

Sohn, Chang Ho ^{[1
,2
]}

Chen, Ritchie ^{[1
,2
]}

McCue, Margaret ^{[1
,2
]}

Yun, Dae Hee ^{[1
,2
]}

Drummond, Gabrielle T. ^{[1
,2
]}

Ku, Taeyun ^{[1
,2
]}

Evans, Nicholas B. ^{[1
,2
]}

Oak, Hayeon Caitlyn ^{[3
]}

Trieu, Wendy ^{[3
]}

Choi, Heejin ^{[1
,2
]}

Jin, Xin ^{[1
,4
,5
]}

Lilascharoen, Varoth ^{[6
]}

Wang, Ji ^{[7
]}

Truttmann, Matthias C. ^{[8
,9
]}

Qi, Helena W. ^{[10
,11
]}

Ploegh, Hidde L. ^{[9
,12
]}

Golub, Todd R. ^{[4
,5
]}

Chen, Shih-Chi ^{[7
]}

Frosch, Matthew P. ^{[9
,13
]}

Kulik, Heather J. ^{[10
]}

Lim, Byung Kook ^{[6
]}

Chung, Kwanghun ^{[1
,2
,3
,4
,5
,10
]}

机构：

[1] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[2] MIT, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[3] MIT, Dept Brain & Cognit Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[4] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA

[5] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[6] Univ Calif San Diego, Div Biol Sci, Neurobiol Sect, La Jolla, CA 92093 USA

[7] Chinese Univ Hong Kong, Dept Mech & Automat Engn, Shatin, Hong Kong, Peoples R China

[8] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA

[9] Harvard Med Sch, Boston, MA USA

[10] MIT, Dept Chem Engn, Cambridge, MA 02139 USA

[11] MIT, Dept Chem, Cambridge, MA 02139 USA

[12] Boston Childrens Hosp, Boston, MA USA

[13] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA

来源：

NATURE BIOTECHNOLOGY | 2019年 / 37卷 / 01期

基金：

美国国家科学基金会;

关键词：

IN-SITU HYBRIDIZATION; MOLECULAR-FORCE FIELD; WHOLE-BODY; BRAIN ACTIVITY; CHAIN-REACTION; INTACT-TISSUE; PROTEIN; RNA; VOLUME; AUTOFLUORESCENCE;

D O I：

10.1038/nbt.4281

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：73 / +

页数：18

共 73 条

[1] The Brain Activity Map [J].

Alivisatos, A. Paul ;

Chun, Miyoung ;

Church, George M. ;

Deisseroth, Karl ;

Donoghue, John P. ;

Greenspan, Ralph J. ;

McEuen, Paul L. ;

Roukes, Michael L. ;

Sejnowski, Terrence J. ;

Weiss, Paul S. ;

Yuste, Rafael .

SCIENCE, 2013, 339 (6125) :1284-1285

[2] Crystal Structure of Enhanced Green Fluorescent Protein to 1.35 Å Resolution Reveals Alternative Conformations for Glu222 [J].

Arpino, James A. J. ;

Rizkallah, Pierre J. ;

Jones, D. Dafydd .

PLOS ONE, 2012, 7 (10)

[3] INCREASED THERMAL-STABILITY OF PROTEINS IN THE PRESENCE OF SUGARS AND POLYOLS [J].

BACK, JF ;

OAKENFULL, D ;

SMITH, MB .

BIOCHEMISTRY, 1979, 18 (23) :5191-5196

[4] Single-molecule super-resolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes [J].

Beliveau, Brian J. ;

Boettiger, Alistair N. ;

Avendano, Maier S. ;

Jungmann, Ralf ;

McCole, Ruth B. ;

Joyce, Eric F. ;

Kim-Kiselak, Caroline ;

Bantignies, Frederic ;

Fonseka, Chamith Y. ;

Erceg, Jelena ;

Hannan, Mohammed A. ;

Hoang, Hien G. ;

Colognori, David ;

Lee, Jeannie T. ;

Shih, William M. ;

Yin, Peng ;

Zhuang, Xiaowei ;

Wu, Chao-ting .

NATURE COMMUNICATIONS, 2015, 6

[5] Nanoscale imaging of RNA with expansion microscopy [J].

Chen, Fei ;

Wassie, Asmamaw T. ;

Cote, Allison J. ;

Sinha, Anubhav ;

Alon, Shahar ;

Asano, Shoh ;

Daugharthy, Evan R. ;

Chang, Jae-Byum ;

Marblestone, Adam ;

Church, George M. ;

Raj, Arjun ;

Boyden, Edward S. .

NATURE METHODS, 2016, 13 (08) :679-+

[6] Expansion microscopy [J].

Chen, Fei ;

Tillberg, Paul W. ;

Boyden, Edward S. .

SCIENCE, 2015, 347 (6221) :543-548

[7] Spatially resolved, highly multiplexed RNA profiling in single cells [J].

Chen, Kok Hao ;

Boettiger, Alistair N. ;

Moffitt, Jeffrey R. ;

Wang, Siyuan ;

Zhuang, Xiaowei .

SCIENCE, 2015, 348 (6233)

[8] Next-Generation in Situ Hybridization Chain Reaction: Higher Gain, Lower Cost, Greater Durability [J].

Choi, Harry M. T. ;

Beck, Victor A. ;

Pierce, Niles A. .

ACS NANO, 2014, 8 (05) :4284-4294

[9] Structural and molecular interrogation of intact biological systems [J].

Chung, Kwanghun ;

Wallace, Jenelle ;

Kim, Sung-Yon ;

Kalyanasundaram, Sandhiya ;

Andalman, Aaron S. ;

Davidson, Thomas J. ;

Mirzabekov, Julie J. ;

Zalocusky, Kelly A. ;

Mattis, Joanna ;

Denisin, Aleksandra K. ;

Pak, Sally ;

Bernstein, Hannah ;

Ramakrishnan, Charu ;

Grosenick, Logan ;

Gradinaru, Viviana ;

Deisseroth, Karl .

NATURE, 2013, 497 (7449) :332-+

[10] Spatially resolved transcriptomics and beyond [J].

Crosetto, Nicola ;

Bienko, Magda ;

van Oudenaarden, Alexander .

NATURE REVIEWS GENETICS, 2015, 16 (01) :57-66

← 1 2 3 4 5 6 7 8 →