From HeLa to human blood: extending single-cell proteomics to the smallest immune cells
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.
Show 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.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.