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

Evan Murray, 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, Hyunjune Sebastian Seung, Kwanghun Chung

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

Summary 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.

Original languageEnglish (US)
Pages (from-to)1500-1514
Number of pages15
JournalCell
Volume163
Issue number6
DOIs
StatePublished - Dec 3 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Murray, E., Cho, J. H., Goodwin, D., Ku, T., Swaney, J., Kim, S. Y., Choi, H., Park, Y. G., Park, J. Y., Hubbert, A., McCue, M., Vassallo, S., Bakh, N., Frosch, M. P., Wedeen, V. J., Seung, H. S., & Chung, K. (2015). Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems. Cell, 163(6), 1500-1514. https://doi.org/10.1016/j.cell.2015.11.025