Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging

Hua Zhang, Yuan Liu, Lauren Fields, Xudong Shi, Penghsuan Huang, Haiyan Lu, Andrew J. Schneider, Xindi Tang, Luigi Puglielli, Nathan V. Welham and Lingjun Li ()
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Hua Zhang: University of Wisconsin-Madison
Yuan Liu: University of Wisconsin-Madison
Lauren Fields: University of Wisconsin-Madison
Xudong Shi: University of Wisconsin-Madison
Penghsuan Huang: University of Wisconsin-Madison
Haiyan Lu: University of Wisconsin-Madison
Andrew J. Schneider: University of Wisconsin-Madison
Xindi Tang: University of Wisconsin-Madison
Luigi Puglielli: University of Wisconsin-Madison
Nathan V. Welham: University of Wisconsin-Madison
Lingjun Li: University of Wisconsin-Madison

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Single-cell (SC) analysis provides unique insight into individual cell dynamics and cell-to-cell heterogeneity. Here, we utilize trapped ion mobility separation coupled with dual-polarity ionization mass spectrometry imaging (MSI) to enable high-throughput in situ profiling of the SC lipidome. Multimodal SC imaging, in which dual-polarity-mode MSI is used to perform serial data acquisition runs on individual cells, significantly enhanced SC lipidome coverage. High-spatial resolution SC-MSI identifies both inter- and intracellular lipid heterogeneity; this heterogeneity is further explicated by Uniform Manifold Approximation and Projection and machine learning-driven classifications. We characterize SC lipidome alteration in response to stearoyl-CoA desaturase 1 inhibition and, additionally, identify cell-layer specific lipid distribution patterns in mouse cerebellar cortex. This integrated multimodal SC-MSI technology enables high-resolution spatial mapping of intercellular and cell-to-cell lipidome heterogeneity, SC lipidome remodeling induced by pharmacological intervention, and region-specific lipid diversity within tissue.

Date: 2023
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DOI: 10.1038/s41467-023-40512-6

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