Authors
Hendriks, I. A., Buch-larsen, S. C., Rykaer, M., Lechner, M. Y., Kverneland, A. H., Arrey, T. N., Hermanson, D., Damoc, E., Olsen, J. V.
Abstract
Single-cell proteomics (SCP) holds the promise of decoding cellular heterogeneity at the functional level, yet achieving deep and reproducible proteome coverage from individual cells has remained a formidable challenge. Here, we established a high-sensitivity, label-free SCP platform that surpasses previous limits in depth and reproducibility. By integrating optimized low-input sample processing, refined liquid chromatography, and the Orbitrap Astral Zoom mass spectrometer, our approach routinely quantified over 7,000 proteins per individual HeLa cell, capturing thousands of low-abundance proteins that eluded prior SCP studies. Applied to very small human peripheral blood mononuclear cells (PBMCs), we identified up to 4,000 proteins per cell, including key markers distinguishing monocytes, T cells, and activated lymphocytes within heterogeneous populations, underscoring that single-cell proteomics can now directly elucidate clinically relevant primary samples with both depth and precision.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 12 Nov 2025.
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