QUAS-R: An SLC1A5-mediated glutamine uptake assay with single-cell resolution reveals metabolic heterogeneity with immune populations

Cell Rep. 2023 Aug 29;42(8):112828. doi: 10.1016/j.celrep.2023.112828. Epub 2023 Jul 19.

Abstract

System-level analysis of single-cell data is rapidly transforming the field of immunometabolism. Given the competitive demand for nutrients in immune microenvironments, there is a need to understand how and when immune cells access these nutrients. Here, we describe a new approach for single-cell analysis of nutrient uptake where we use in-cell biorthogonal labeling of a functionalized amino acid after transport into the cell. In this manner, the bona fide active uptake of glutamine via SLC1A5/ASCT2 could be quantified. We used this assay to interrogate the transport capacity of complex immune subpopulations, both in vitro and in vivo. Taken together, our findings provide an easy sensitive single-cell assay to assess which cells support their function via SLC1A5-mediated uptake. This is a significant addition to the single-cell metabolic toolbox required to decode the metabolic landscape of complex immune microenvironments.

Keywords: CP: Immunology; CP: Metabolism; SLC1A5; amino acid transport; glutamine uptake; lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids* / metabolism
  • Biological Transport
  • Cell Line, Tumor
  • Cell Proliferation
  • Glutamine* / metabolism
  • Minor Histocompatibility Antigens / metabolism

Substances

  • Glutamine
  • Amino Acids
  • Minor Histocompatibility Antigens