摘要：SummaryAdvances in single cell genomics and transcriptomics have shown that at tissue level there is complex cellular heterogeneity. To understand the effect of this inter-cell heterogeneity on metabolism it is essential to develop a single cell lipid profiling approach that allows the measurement of lipids in large numbers of single cells from a population. This will provide a functional readout of cell activity and membrane structure. Using liquid extraction surface analysis coupled with high-resolution mass spectrometry we have developed a high-throughput method for untargeted single cell lipid profiling. This technological advance highlighted the importance of cellular heterogeneity in the functional metabolism of individual human dopamine neurons, suggesting that A53T alpha-synuclein (SNCA) mutant neurons have impaired membrane function. These results demonstrate that this single cell lipid profiling platform can provide robust data that will expand the frontiers in biomedical research.Graphical AbstractDisplay OmittedHighlights•Combining FACS and LESA-MS to establish high-throughput single cell lipid profiling•Lipid differences found within and between populations of human dopamine neurons•Inter-cell lipid heterogeneity is increased inSNCA-A53Tdopamine neurons•Identification and isolation of human iPSC-dopamine neurons with a TH-RFP reporterMolecular Neuroscience; Cellular Neuroscience ; Lipidomics ; Metabolomics
