Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging.
Hua ZhangYuan LiuLauren FieldsXudong ShiPenghsuan HuangHaiyan LuAndrew J SchneiderXindi TangLuigi PuglielliNathan V WelhamLingjun LiPublished in: Nature communications (2023)
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.
Keyphrases
- single cell
- rna seq
- high resolution
- high throughput
- mass spectrometry
- machine learning
- cell therapy
- randomized controlled trial
- magnetic resonance imaging
- pain management
- liquid chromatography
- stem cells
- bone marrow
- oxidative stress
- deep learning
- signaling pathway
- artificial intelligence
- mesenchymal stem cells
- single molecule
- reactive oxygen species
- functional connectivity
- capillary electrophoresis