Multimodal mass spectrometry imaging reveals molecular, cellular and structural organization of mammalian liver at single cell resolution
The spatial organization of heterogeneous cell population within the complex biometrics in tissue content drive distinct biological functions. To delineate the complicity, multiple spatial omics are required to probe the multi-level biomolecules and their interaction. However, there is a lack of approach to integrating the different biomolecules in the same tissue sample at the single cell level due to the incompatibility of sample preparation and single omics-oriented technology. Mass spectrometry imaging (IMS) has enabled label-free, untargeted spatial measurement of endogenous lipids, metabolites, and proteins at multi-scale resolution. We have combined multimodal novel IMS at multiple scales to image highly complementary molecular information to correlate the metabolomic, lipidomic and proteomic in single cell level on the same liver tissue. Desorption electrospray ionization (DESI)-IMS is employed to map metabolic heterogeneity at the tissue level with spatial resolution of 40 µm. The area of liver lobule with diverse metabolic activities is then imaged by a novel IMS, water gas cluster ion beam (GCIB) and C60 beam secondary ion mass spectrometry (H2O)n-GCIB-SIMS &C60-SIMS at spatial resolution 1~3 µm, integrating the untargeted metabolites/lipids and targeted proteins in the same individual liver cells directly on the tissue to delineate the metabolic state of different type of cells. DESI-MSI revealed metabolites such as taurine, uric acid and ascorbic acid as well as glycine and taurine conjugated bile acids localized in periportal zones in both mouse and human liver. Similarly, free fatty acids, glycerolipids, and phospholipids showed distinct distribution patterns in mouse and human livers. At the subcellular level, two SIMS modalities uncovered distinct lipid clusters around the periportal and pericentral veins, metabolic/lipidomic signatures of liver cells (e.g., sinusoidal, Kupffer, hepatocytes, Ito stellate, diverse immune cells). Moreover, the clustering analysis demonstrates for the first time that the metabolites/lipids can be used to classify the cell types resembling to cell protein markers. Spatially resolved IMS analysis revealed metabolic zonation within anatomical structures and its heterogeneity corresponding to cellular composition and organization within the histologically homogeneous tissue, the liver. The multimodal imaging pipeline we present provides a more comprehensive view of spatial biology and leads to an improving understanding of healthy and pathophysiological states.
The datasets are publicly available accompanying our publication entitled 'Multimodal mass spectrometry imaging reveals molecular, cellular and structural organization of mammalian liver at single-cell resolution'.
The imaging mass spectrometry datasets can be analyzed using the software Ionoptika Analyser (Link for download: http://downloads.ionoptika.net/ImageAnalyser2D/IonoptikaImageAnalyser2D_amd64_2_0_2_1.iso).
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|Work Title||Multimodal mass spectrometry imaging reveals molecular, cellular and structural organization of mammalian liver at single cell resolution|
|Subtitle||Multimodal SIMS imaging of mouse/human liver|
|License||CC0 1.0 (Public Domain Dedication)|
|Publication Date||April 8, 2022|
|Deposited||April 08, 2022|
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