Developing Single-Cell Proteomics to Open New Perspectives on Biology

Abstract Mass-spectrometry-based single-cell proteomics has evolved from an unconventional idea into a rapidly advancing technology that is opening new perspectives on biology. In this perspective, I reflect on the development of the field over the past decade: the guiding ideas, the early experiments that established feasibility, the advances in sample preparation, mass spectrometry methods, instrumentation, computation, and multiplexing that transformed sensitivity and throughput, and the collaborative efforts that made these technologies increasingly reproducible and accessible. I highlight biological results from the first decade and questions that have become addressable with highly quantitative protein measurements in individual cells, including functional protein coordination, regulation of protein synthesis and degradation, developmental decisions, and disease progression. Looking forward, I foresee that continued technological innovation, rigorous benchmarking, and an open and critically engaged community will be essential for realizing the broader promise of single-cell proteomics: turning high resolution protein analysis into a powerful source of biological insight, including generalizable principles.