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

Cell
Authors
Keywords
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.

Year of Publication
2015
Journal
Cell
Volume
163
Issue
6
Pages
1500-14
Date Published
2015 Dec 03
ISSN
1097-4172
URL
DOI
10.1016/j.cell.2015.11.025
PubMed ID
26638076
PubMed Central ID
PMC5275966
Links
Grant list
U01 NS090473 / NS / NINDS NIH HHS / United States
5 P50 AG005134 / AG / NIA NIH HHS / United States
P50 AG005134 / AG / NIA NIH HHS / United States
DP2 ES027992 / ES / NIEHS NIH HHS / United States
1-U01-NS090473-01 / NS / NINDS NIH HHS / United States
T32 EB019940 / EB / NIBIB NIH HHS / United States