High‐Throughput Single‐Cell Mass Spectrometry Reveals Abnormal Lipid Metabolism in Pancreatic Ductal Adenocarcinoma. (11th October 2021)

• Record Type: Journal Article
• Authors: Liu, Qinlei; Ge, Wenjie; Wang, Tongtong; Lan, Jiayi; Martínez‐Jarquín, Sandra; Wolfrum, Christian; Stoffel, Markus; Zenobi, Renato
• Is Part Of: Angewandte Chemie. Volume 133:Number 46(2021)
• Page Start: 24739
• Page End: 24747
• Publication Date: 2021-10-11
• Subjects: ATP citrate lyase -- dielectric barrier discharge -- ionization sources -- lipid metabolism -- single-cell mass spectrometry; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202107223
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Even populations of clonal cells are heterogeneous, which requires high‐throughput analysis methods with single‐cell sensitivity. Here, we propose a rapid, label‐free single‐cell analytical method based on active capillary dielectric barrier discharge ionization mass spectrometry, which can analyze multiple metabolites in single cells at a rate of 38 cells/minute. Multiple cell types (HEK‐293T, PANC‐1, CFPAC‐1, H6c7, HeLa and iBAs) were discriminated successfully. We found evidence for abnormal lipid metabolism in pancreatic cancer cells. We also analyzed gene expression in a cancer genome atlas dataset and found that the mRNA level of a critical enzyme of lipid synthesis (ATP citrate lyase, ACLY) was upregulated in human pancreatic ductal adenocarcinoma (PDAC). Moreover, both an ACLY chemical inhibitor and a siRNA approach targeting ACLY could suppress the viability of PDAC cells. A significant reduction in lipid content in treated cells indicates that ACLY could be a potential target for treating pancreatic cancer. Abstract : A high‐throughput and label‐free single‐cell mass spectrometric method based on a dielectric barrier discharge ionization source was used to analyze multiple metabolites in different cell types (HEK‐293T, PANC‐1, CFPAC‐1, H6c7, HeLa and iBAs) at the single‐cell level with a throughput of around 38 cells per minute.