Development and Application of High-Throughput Single Cell Lipid Profiling: A Study of SNCA-A53T Human Dopamine Neurons
Stuart G. Snowden,
Hugo J.R. Fernandes,
Josh Kent,
Stefanie Foskolou,
Peri Tate,
Sarah F. Field,
Emmanouil Metzakopian,
Albert Koulman
Affiliations
Stuart G. Snowden
Core Metabolomics and Lipidomics Laboratory, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Level 4 Pathology, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; Department of Biological Sciences, Royal Holloway University of London, Egham, Surrey Tw20 0EX, UK
Hugo J.R. Fernandes
UK Dementia Research Institute, University of Cambridge, Department of Clinical Neurosciences, Cambridge Biomedical Campus, Cambridge CB2 0AH, UK
Josh Kent
Core Metabolomics and Lipidomics Laboratory, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Level 4 Pathology, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; UK Dementia Research Institute, University of Cambridge, Department of Clinical Neurosciences, Cambridge Biomedical Campus, Cambridge CB2 0AH, UK
Stefanie Foskolou
UK Dementia Research Institute, University of Cambridge, Department of Clinical Neurosciences, Cambridge Biomedical Campus, Cambridge CB2 0AH, UK
Peri Tate
Department of Biological Sciences, Royal Holloway University of London, Egham, Surrey Tw20 0EX, UK
Sarah F. Field
UK Dementia Research Institute, University of Cambridge, Department of Clinical Neurosciences, Cambridge Biomedical Campus, Cambridge CB2 0AH, UK
Emmanouil Metzakopian
UK Dementia Research Institute, University of Cambridge, Department of Clinical Neurosciences, Cambridge Biomedical Campus, Cambridge CB2 0AH, UK; Corresponding author
Albert Koulman
Core Metabolomics and Lipidomics Laboratory, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Level 4 Pathology, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; Corresponding author
Summary: 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 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.
