Single-Cell Mass Spectrometry Approaches to Explore Cellular Heterogeneity

Area of Science:

• Biochemistry
• Analytical Chemistry
• Cell Biology

Background:

• Cellular heterogeneity is key to understanding cell populations.
• Single-cell analysis provides molecular insights (genomic, transcriptomic, proteomic, metabolomic).
• Mass spectrometry (MS) is a label-free technique for multiplexed analysis of biomolecules in single cells.

Purpose of the Study:

• To review recent advancements in single-cell mass spectrometry (MS) techniques.
• To highlight methods for sampling and ionization of volume-limited samples.
• To discuss challenges and considerations for single-cell MS analysis.

Main Methods:

• Focus on sampling and ionization techniques for single cells.
• Exploration of sample treatment, separation, and data analysis strategies.
• Emphasis on label-free multiplexed analysis of proteins, peptides, lipids, and metabolites.

Main Results:

• Recent advances enable multiplexed analysis of molecular classes in individual cells.
• Abundances of molecular classes correlate with cellular physiological states and environmental responses.
• Specific strategies are being developed for volume-limited samples in single-cell MS.

Conclusions:

• Single-cell MS is a powerful tool for dissecting cellular heterogeneity.
• Addressing challenges like subcellular heterogeneity and data analysis is crucial for future progress.
• High-throughput, high molecular coverage, and minimal perturbation are key goals for single-cell MS development.