The Intriguing Landscape of Single-Cell Protein Analysis.

Profiling protein expression at single-cell resolution is essential for fundamental biological research (such as cell differentiation and tumor microenvironmental examination) and clinical precision medicine where only a limited number of primary cells are permitted. With the recent advances in engineering, chemistry, and biology, single-cell protein analysis methods are developed rapidly, which enable high-throughput and multiplexed protein measurements in thousands of individual cells. In combination with single cell RNA sequencing and mass spectrometry, single-cell multi-omics analysis can simultaneously measure multiple modalities including mRNAs, proteins, and metabolites in single cells, and obtain a more comprehensive exploration of cellular signaling processes, such as DNA modifications, chromatin accessibility, protein abundance, and gene perturbation. Here, the recent progress and applications of single-cell protein analysis technologies in the last decade are summarized. Current limitations, challenges, and possible future directions in this field are also discussed.