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Cell. 2015 Dec 3;163(6):1500-14. doi: 10.1016/j.cell.2015.11.025.

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

Author information

1
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Simons Center for Data Analysis, 160 Fifth Avenue, 8th Floor, New York, NY 10010, USA.
4
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
5
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
6
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
7
C.S. Kubik Laboratory of Neuropathology, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
8
Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
9
Simons Center for Data Analysis, 160 Fifth Avenue, 8th Floor, New York, NY 10010, USA; Princeton Neuroscience Institute and Computer Science Department, Princeton University, Princeton, NJ 08544, USA.
10
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: khchung@mit.edu.

Abstract

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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PMID:
26638076
PMCID:
PMC5275966
DOI:
10.1016/j.cell.2015.11.025
[Indexed for MEDLINE]
Free PMC Article

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