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Development and application of high-throughput single cell lipid profiling: a study of SNCA-A53T human dopamine neurons

Accepted version
Peer-reviewed

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Type

Article

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Authors

Snowden, stuart 
Fernandes, Hugo JR 
Kent, Josh 
Foskolou, Stefanie 
Tate, Per 

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 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.

Description

Keywords

Cellular Neuroscience, Lipidomics, Metabolomics, Molecular Neuroscience

Journal Title

iScience

Conference Name

Journal ISSN

2589-0042
2589-0042

Volume Title

Publisher

Elsevier

Rights

All rights reserved
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/P028195/1)
Michael J. Fox Foundation (MJFF) (MJFF 16486)
MRC (MC_UU_00014/5)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_PC_12012)
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).