High-Throughput Single-Cell Mass Spectrometry Reveals Abnormal Lipid Metabolism in Pancreatic Ductal Adenocarcinoma

Angew Chem Int Ed Engl. 2021 Nov 8;60(46):24534-24542. doi: 10.1002/anie.202107223. Epub 2021 Oct 11.


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.

Keywords: ATP citrate lyase; dielectric barrier discharge; ionization sources; lipid metabolism; single-cell mass spectrometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Citrate (pro-S)-Lyase / antagonists & inhibitors
  • ATP Citrate (pro-S)-Lyase / genetics
  • ATP Citrate (pro-S)-Lyase / metabolism
  • Carcinoma, Ductal / metabolism
  • Carcinoma, Ductal / pathology
  • Cell Line, Tumor
  • Cell Survival
  • Discriminant Analysis
  • HEK293 Cells
  • High-Throughput Screening Assays / methods*
  • Humans
  • Lipids / analysis*
  • Lipids / biosynthesis
  • Mass Spectrometry* / methods
  • Metabolome*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Single-Cell Analysis


  • Lipids
  • RNA, Small Interfering
  • ATP Citrate (pro-S)-Lyase