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Updated: Jun 27, 2025
Author Spotlight: Advancing Metabolomics Analysis of Rare Hematopoietic Stem Cells
Published on: February 23, 2024
Cell metabolism: Functional and phenotypic single cell approaches
Sara De Biasi1, Julien Paul Gigan2, Rebecca Borella1
1Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
Insights
Investigating immunometabolism is crucial for understanding immune dysfunction. Single-cell technologies now allow detailed analysis of individual immune cell metabolism, offering new insights into mitochondrial function and cellular metabolism.
Area of Science:
- Immunology and Metabolism
- Cellular Biology
Background:
- Immune cell function relies on metabolic pathways; dysregulation leads to immune dysfunction.
- Deviations in immune cell metabolic states (hypermetabolism/hypometabolism) are linked to diseases like autoimmunity, infections, and cancer.
- Traditional bulk analysis methods limit detailed immunometabolism studies.
Purpose of the Study:
- To provide an overview of single-cell approaches for studying immunometabolism.
- To detail methods for investigating mitochondrial function and metabolic dependence in immune cells.
- To guide the selection of appropriate experimental settings for studying cell metabolism.
Main Methods:
- Overview of single-cell technologies: multiparameter flow cytometry, mass cytometry, and RNA cytometry.
- Focus on methods measuring mitochondrial functions and metabolic dependence.
- Discussion of experimental settings, strengths, and weaknesses of various approaches.
Main Results:
- Single-cell technologies enable precise measurement of individual immune cell metabolic states.
- These methods can be applied to diverse samples from basic, translational, and clinical research.
- The study outlines how to choose optimal approaches for specific research questions.
Conclusions:
- Single-cell technologies revolutionize immunometabolism research by enabling high-resolution analysis.
- Understanding immune cell metabolism at the single-cell level is key to addressing immune dysfunction.
- This review aids researchers in selecting and applying single-cell methods for studying immunometabolism.
Abstract:
Several metabolic pathways are essential for the physiological regulation of immune cells, but their dysregulation can cause immune dysfunction. Hypermetabolic and hypometabolic states represent deviations in the magnitude and flexibility of effector cells in different contexts, for example in autoimmunity, infections or cancer. To study immunometabolism, most methods focus on bulk populations and rely on in vitro activation assays. Nowadays, thanks to the development of single-cell technologies, including multiparameter flow cytometry, mass cytometry, RNA cytometry, among others, the metabolic state of individual immune cells can be measured in a variety of samples obtained in basic, translational and clinical studies. Here, we provide an overview of different single-cell approaches that are employed to investigate both mitochondrial functions and cell dependence from mitochondria metabolism. Moreover, besides the description of the appropriate experimental settings, we discuss the strengths and weaknesses of different approaches with the aim to suggest how to study cell metabolism in the settings of interest.
