Development and application of high-throughput single cell lipid profiling: a study of SNCA-A53T human dopamine neurons
Fernandes, Hugo JR
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Snowden, s., Fernandes, H. J., Kent, J., Foskolou, S., Tate, P., Field, S., Metzakopian, E., & et al. (2020). Development and application of high-throughput single cell lipid profiling: a study of SNCA-A53T human dopamine neurons. iScience https://doi.org/10.1016/j.isci.2020.101703
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 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.
This work was supported by the Michael J Fox Foundation grant ID 16486. Stuart G. Snowden was also supported by the BBSRC (BB/P028195/1) and Albert Koulman by the National Institute of Health Research Cambridge Biomedical Research Centre (146281). Emmanouil Metzakopian is funded by UK DRI grant ID RRZA/175. Hugo J. R. Fernandes is funded by Open Targets (OTAR035).
Michael J. Fox Foundation (MJFF) (MJFF 16486)
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External DOI: https://doi.org/10.1016/j.isci.2020.101703
This record's URL: https://www.repository.cam.ac.uk/handle/1810/311782
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