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).

This license below will allow anyone who wants to look at your data to use Analyse for up to 7 days. User name OPENDATA License IA2D-1T10-2020-0407-F0A8-A59A-9CE6 Activations limit 99 Activations remaining 99

Please contact Ionoptika if you wish to use the software beyond 7 days via our Support e-mail (support@ionoptika.co.uk)

Files

Metadata

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
Access
Open Access
Creators
  1. Hua Tian
Keyword
  1. Multimodal mass spectrometry imaging
  2. Water gas cluster ion beam secondary ion mass spectrometry [(H2O)n-GCIB-SIMS]
  3. C60 secondary ion mass spectrometry
  4. Lipidomics
  5. Metabolomics
  6. Proteomics
  7. Single cell resolution
License CC0 1.0 (Public Domain Dedication)
Work Type Dataset
Publication Date April 8, 2022
DOI doi:10.26207/6a38-tr35
Related URLs
Deposited April 08, 2022

Versions

Analytics

Collections

This resource is currently not in any collection.

Work History

Version 1
published

  • Created
  • Updated
  • Updated
  • Added Creator Hua Tian
  • Added 2021_Apr_24th_Sat_20_41_20_Mouse liver S5 R2 H2O 30k neg.zip
  • Added 2021_Jul_19th_Mon_20_52_17_3D S10 R1 H2O 30k neg.zip
  • Added 2021_Apr_10th_Sat_22_39_10_MOuse S1 R2 79kV H2O28k neg.zip
  • Added 2021_Apr_14th_Wed_11_06_11_Mouse liver S1 R2 C60 pos.zip
  • Added 2021_Aug_08th_Sun_20_10_18_S10 R1 2nd C60 pos.zip
  • Added 2021_Apr_25th_Sun_20_32_24_Mouse liver S5 R2 C60 pos.zip
  • Deleted 2021_Apr_10th_Sat_22_39_10_MOuse S1 R2 79kV H2O28k neg.zip
  • Deleted 2021_Apr_14th_Wed_11_06_11_Mouse liver S1 R2 C60 pos.zip
  • Deleted 2021_Apr_24th_Sat_20_41_20_Mouse liver S5 R2 H2O 30k neg.zip
  • Deleted 2021_Apr_25th_Sun_20_32_24_Mouse liver S5 R2 C60 pos.zip
  • Deleted 2021_Aug_08th_Sun_20_10_18_S10 R1 2nd C60 pos.zip
  • Deleted 2021_Jul_19th_Mon_20_52_17_3D S10 R1 H2O 30k neg.zip
  • Added 2021_Apr_10th_Sat_22_39_10_MOuse S1 R2 79kV H2O28k neg.zip
  • Added 2021_Apr_14th_Wed_11_06_11_Mouse liver S1 R2 C60 pos.zip
  • Added 2021_Apr_24th_Sat_20_41_20_Mouse liver S5 R2 H2O 30k neg.zip
  • Added 2021_Jul_19th_Mon_20_52_17_3D S10 R1 H2O 30k neg.zip
  • Added 2021_Apr_25th_Sun_20_32_24_Mouse liver S5 R2 C60 pos.zip
  • Added 2021_Aug_08th_Sun_20_10_18_S10 R1 2nd C60 pos.zip
  • Updated Publisher's Statement, License Show Changes
    Publisher's Statement
    • 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 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).
    • This license below will allow anyone who wants to look at your data to use Analyse for up to 7 days.
    • User name OPENDATA
    • License IA2D-1T10-2020-0407-F0A8-A59A-9CE6
    • Activations limit 99
    • Activations remaining 99
    • Please contact Ionoptika if you wish to use the software beyond 7 days via our Support e-mail (support@ionoptika.co.uk)
    License
    • http://creativecommons.org/publicdomain/zero/1.0/
  • Published
  • Updated Keyword, Description, Related URLs, and 1 more Show Changes
    Keyword
    • Multimodal mass spectrometry imaging ; Water gas cluster ion beam secondary ion mass spectrometry [(H2O)n-GCIB-SIMS]; C60 secndary ion mass spectrometry; lipidomics; metabolomics; proteomics; single cell resolution
    • Multimodal mass spectrometry imaging, Water gas cluster ion beam secondary ion mass spectrometry [(H2O)n-GCIB-SIMS], C60 secondary ion mass spectrometry, Lipidomics, Metabolomics, Proteomics, Single cell resolution
    Description
    • 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 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).
    • This license below will allow anyone who wants to look at your data to use Analyse for up to 7 days.
    • User name OPENDATA
    • License IA2D-1T10-2020-0407-F0A8-A59A-9CE6
    • Activations limit 99
    • Activations remaining 99
    • Please contact Ionoptika if you wish to use the software beyond 7 days via our Support e-mail (support@ionoptika.co.uk)
    Related URLs
    • https://doi.org/10.1016/j.devcel.2024.01.025, https://doi.org/10.1101/2022.09.26.508878
    Publisher's Statement
    • 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).
    • This license below will allow anyone who wants to look at your data to use Analyse for up to 7 days.
    • User name OPENDATA
    • License IA2D-1T10-2020-0407-F0A8-A59A-9CE6
    • Activations limit 99
    • Activations remaining 99
    • Please contact Ionoptika if you wish to use the software beyond 7 days via our Support e-mail (support@ionoptika.co.uk)