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Laser cleavable probes for in situ multiplexed glycan detection by single cell mass spectrometry.

ABSTRACT: Glycans binding on the cell surface through glycosylation play a key role in controlling various cellular processes, and glycan analysis at a single-cell level is necessary to study cellular heterogeneity and diagnose diseases in the early stage. Herein, we synthesized a series of laser cleavable probes, which could sensitively detect glycans on single cells and tissues by laser desorption ionization mass spectrometry (LDI-MS). This multiplexed and quantitative glycan detection was applied to evaluate the alterations of four types of glycans on breast cancer cells and drug-resistant cancer cells at a single-cell level, indicating that drug resistance may be related to the upregulation of glycan with a β-d-galactoside (Galβ) group and Neu5Aca2-6Gal(NAc)-R. Moreover, the glycan spatial distribution in cancerous and paracancerous human tissues was also demonstrated by MS imaging, showing that glycans are overexpressed in cancerous tissues. Therefore, this single-cell MS approach exhibits promise for application in studying glycan functions which are essential for clinical biomarker discovery and diagnosis of related diseases.

SUBMITTER: Han J

PROVIDER: S-EPMC7066667 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Correction: Laser cleavable probes for <i>in situ</i> multiplexed glycan detection by single cell mass spectrometry.

Project description:[This corrects the article DOI: 10.1039/C9SC03912K.].

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Project description:Glycans are crucial for many key biological processes and their alterations are often a hallmark of disease. Thus, multiplexed and sensitive analysis of glycans is of intense interest. Here we report a novel approach using DNA-mediated cell surface engineering for glycan profiling by MALDI-TOF mass spectrometry (MS). Following lectin binding, DNA amplification and hybridization, glycans on the cell surface are specifically labeled by short DNA probes, which can be facilely released, ionized and detected in MALDI-TOF MS. This strategy converts the analysis of glycans to the detection of DNA probes, overcoming the complicated composition and low ionization efficiency of glycans, enabling in situ detection and facilitating multiplex analysis. The amplification procedure also improves the sensitivity. This approach has been applied to evaluate glycomic alterations in cancer cells and provided the intrinsic distribution of glycans in tissues using MALDI imaging mass spectrometry.

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