Journal
CELL
Volume 163, Issue 6, Pages 1500-1514Publisher
CELL PRESS
DOI: 10.1016/j.cell.2015.11.025
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Funding
- Simons Postdoctoral Fellowship
- Life Sciences Research Foundation
- Burroughs Wellcome Fund Career Awards at the Scientific Interface
- Searle Scholars Program
- Michael J. Fox Foundation
- DARPA
- JPB Foundation (PIIF and PNDRF)
- NIH [1-U01-NS090473-01]
- Massachusetts Alzheimer Disease Research Center [5 P50 AG005134]
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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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