Signal Amplification by Cyclic Extension Enables High-sensitivity Single-cell Mass Cytometry

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2024 Jul 29

PMID 39075149

Authors

Xiao-Kang Lun

Kuanwei Sheng

Xueyang Yu

Ching Yeung Lam

Gokul Gowri

Matthew Serrata

Yunhao Zhai

Hanquan Su

Jingyi Luan

Youngeun Kim

Donald E Ingber

Hartland W Jackson

Michael B Yaffe

Peng Yin

Affiliations

Soon will be listed here.

Abstract

Mass cytometry uses metal-isotope-tagged antibodies to label targets of interest, which enables simultaneous measurements of ~50 proteins or protein modifications in millions of single cells, but its sensitivity is limited. Here, we present a signal amplification technology, termed Amplification by Cyclic Extension (ACE), implementing thermal-cycling-based DNA in situ concatenation in combination with 3-cyanovinylcarbazole phosphoramidite-based DNA crosslinking to enable signal amplification simultaneously on >30 protein epitopes. We demonstrate the utility of ACE in low-abundance protein quantification with suspension mass cytometry to characterize molecular reprogramming during the epithelial-to-mesenchymal transition as well as the mesenchymal-to-epithelial transition. We show the capability of ACE to quantify the dynamics of signaling network responses in human T lymphocytes. We further present the application of ACE in imaging mass cytometry-based multiparametric tissue imaging to identify tissue compartments and profile spatial aspects related to pathological states in polycystic kidney tissues.

Citing Articles

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Xu X, Su J, Zhu R, Li K, Zhao X, Fan J Mol Cancer. 2025; 24(1):63.

PMID: 40033282 PMC: 11874780. DOI: 10.1186/s12943-025-02240-x.

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