Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging
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 lipido...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40512-6 |
| _version_ | 1797558034601345024 |
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| author | Hua Zhang Yuan Liu Lauren Fields Xudong Shi Penghsuan Huang Haiyan Lu Andrew J. Schneider Xindi Tang Luigi Puglielli Nathan V. Welham Lingjun Li |
| author_facet | Hua Zhang Yuan Liu Lauren Fields Xudong Shi Penghsuan Huang Haiyan Lu Andrew J. Schneider Xindi Tang Luigi Puglielli Nathan V. Welham Lingjun Li |
| author_sort | Hua Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:24:43Z |
| format | Article |
| id | doaj.art-c5590947bef34f65b5fde66ebc7f6df8 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:24:43Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-c5590947bef34f65b5fde66ebc7f6df82023-11-20T10:14:05ZengNature PortfolioNature Communications2041-17232023-08-0114111110.1038/s41467-023-40512-6Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imagingHua Zhang0Yuan Liu1Lauren Fields2Xudong Shi3Penghsuan Huang4Haiyan Lu5Andrew J. Schneider6Xindi Tang7Luigi Puglielli8Nathan V. Welham9Lingjun Li10School of Pharmacy, University of Wisconsin-MadisonSchool of Pharmacy, University of Wisconsin-MadisonDepartment of Chemistry, University of Wisconsin-MadisonDivision of Otolaryngology, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-MadisonDepartment of Chemistry, University of Wisconsin-MadisonSchool of Pharmacy, University of Wisconsin-MadisonDepartment of Medicine, University of Wisconsin-MadisonDepartment of Chemistry, University of Wisconsin-MadisonDepartment of Medicine, University of Wisconsin-MadisonDivision of Otolaryngology, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-MadisonSchool of Pharmacy, University of Wisconsin-MadisonAbstract 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.https://doi.org/10.1038/s41467-023-40512-6 |
| spellingShingle | Hua Zhang Yuan Liu Lauren Fields Xudong Shi Penghsuan Huang Haiyan Lu Andrew J. Schneider Xindi Tang Luigi Puglielli Nathan V. Welham Lingjun Li Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging Nature Communications |
| title | Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging |
| title_full | Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging |
| title_fullStr | Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging |
| title_full_unstemmed | Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging |
| title_short | Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging |
| title_sort | single cell lipidomics enabled by dual polarity ionization and ion mobility mass spectrometry imaging |
| url | https://doi.org/10.1038/s41467-023-40512-6 |
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