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Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems

 Evan Murraya  ;  Jae Hun Cho  ;  Daniel Goodwin  ;  Taeyun Ku  ;  Justin Swaney  ;  Sung-Yon Kim  ;  Heejin Choi  ;  Young-Gyun Park  ;  Jeong-Yoon Park  ;  Austin Hubbert  ;  Margaret McCue  ;  Sara Vassallo  ;  Naveed Bakh  ;  Matthew P. Frosch  ;  Van J. Wedeen  ;  H. Sebastian Seung  ;  Kwanghun Chung 
 CELL, Vol.163(6) : 1500-1514, 2015 
Journal Title
Issue Date
Algorithms ; Animals ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Imaging/methods* ; Nerve Fibers, Myelinated/chemistry ; Proteomics ; Reducing Agents ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tissue Preservation/methods*
Combined measurement of diverse molecular and anatomical traits that span multiple levels remains a major challenge in biology. Here, we introduce a simple method that enables proteomic imaging for scalable, integrated, high-dimensional phenotyping of both animal tissues and human clinical samples. This method, termed SWITCH, uniformly secures tissue architecture, native biomolecules, and antigenicity across an entire system by synchronizing the tissue preservation reaction. The heat- and chemical-resistant nature of the resulting framework permits multiple rounds (>20) of relabeling. We have performed 22 rounds of labeling of a single tissue with precise co-registration of multiple datasets. Furthermore, SWITCH synchronizes labeling reactions to improve probe penetration depth and uniformity of staining. With SWITCH, we performed combinatorial protein expression profiling of the human cortex and also interrogated the geometric structure of the fiber pathways in mouse brains. Such integrated high-dimensional information may accelerate our understanding of biological systems at multiple levels.
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1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Park, Jeong Yoon(박정윤) ORCID logo https://orcid.org/0000-0002-3728-7784
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