Single-cell Proteomics: Deciphering Protein Turnover in Mammalian Cells

Abstract

Single-cell technologies have revolutionized modern biology, with early advances driven primarily by high-throughput sequencing and imaging platforms. Among emerging approaches, single-cell proteomics has gained considerable attention because proteins represent the principal functional effectors of cellular physiology. Protein turnover, the dynamic equilibrium between protein synthesis and degradation, is fundamental to maintaining cellular homeostasis, regulating signalling pathways, and preserving cell viability. Over the past decade and particularly in the last five years, substantial technological progress has accelerated the development of single-cell proteomics, despite the intrinsic analytical challenges posed by the lack of protein amplification strategies comparable to those available for nucleic acids. Increasing evidence demonstrates that single-cell proteomics provides critical complementary information to single-cell transcriptomics, enabling a more comprehensive understanding of cellular function and heterogeneity. This review summarizes the current landscape of single-cell proteomics and key biological applications. It highlights recent advances that enable sensitive analysis of protein turnover dynamics in individual cells and complex populations, as well as major technical and computational challenges, including limited sample volumes, sensitivity, reproducibility, and normalization.