posted on 2021-06-02, 12:06authored byHua Tian, Louis J. Sparvero, Tamil Selvan Anthonymuthu, Wan-Yang Sun, Andrew A. Amoscato, Rong-Rong He, Hülya Bayır, Valerian E. Kagan, Nicholas Winograd
The temporo-spatial
organization of different cells in the tumor
microenvironment (TME) is the key to understanding their complex communication
networks and the immune landscape that exists within compromised tissues.
Multi-omics profiling of single-interacting cells in the native TME
is critical for providing further information regarding the reprograming
mechanisms leading to immunosuppression and tumor progression. This
requires new technologies for biomolecular profiling of phenotypically
heterogeneous cells on the same tissue sample. Here, we developed
a new methodology for comprehensive lipidomic and metabolomic profiling
of individual cells on frozen-hydrated tissue sections using water
gas cluster ion beam secondary ion mass spectrometry ((H2O)n-GCIB-SIMS) (at 1.6 μm beam
spot size), followed by profiling cell-type specific lanthanide antibodies
on the same tissue section using C60-SIMS (at 1.1 μm
beam spot size). We revealed distinct variations of distribution and
intensities of >150 key ions (e.g., lipids and important metabolites)
in different types of the TME individual cells, such as actively proliferating
tumor cells as well as infiltrating immune cells. The demonstrated
feasibility of SIMS imaging to integrate the multi-omics profiling
in the same tissue section at the single-cell level will lead to new
insights into the role of lipid reprogramming and metabolic response
in normal regulation or pathogenic discoordination of cell–cell
interactions in a variety of tissue microenvironments.