期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 46, 页码 24534-24542出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202107223
关键词
ATP citrate lyase; dielectric barrier discharge; ionization sources; lipid metabolism; single-cell mass spectrometry
资金
- China Scholarship Council (CSC) [201906240053]
- Eidgenossische Technische Hochschule Zurich
A rapid, label-free single-cell analysis method based on mass spectrometry was proposed, allowing for efficient analysis of metabolites and successful discrimination of multiple cell types. Evidence of abnormal lipid metabolism in pancreatic cancer cells was found, indicating a potential therapeutic target.
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.
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