Top-down Proteomics of 10,000 Single Brain Cells

We introduce single-cell Proteoform imaging Mass Spectrometry ( scPiMS ), which realizes the benefit of direct analysis of intact proteins to process 10,836 single cells from the rat hippocampus. This new platform addresses the throughput bottleneck for single cell proteomics using mass spectrometry, boosting cell processing rates by >20-fold in the field. We identified 169 proteoforms <70 kDa from single brain cells and classified 2758 of them as neurons, astrocytes or microglia cell types. ### Competing Interest Statement N.L.K. and J.O.K. report a conflict of interest with I2MS technology, being commercialized by Thermo Fisher Scientific.