Abstract

Advances 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 read out of cell activity and membrane structure. Using liquid extraction surface analysis (LESA) coupled with high-resolution mass spectrometry we have developed a new high-throughput method for untargeted single cell lipid profiling. This technological advance revealed new insights into 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 novel single cell lipid profiling platform can provide robust data that will open new frontiers in biomedical research.

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