Department of Chemistry, Pennsylvania State University, Chemistry Building, Shortlidge Rd, University Park, Pennsylvania 16802, United States.
Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health, University of Pittsburgh, PUBHL A-420, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261, United States.
Anal Chem. 2021 Jun 15;93(23):8143-8151. doi: 10.1021/acs.analchem.0c05311. Epub 2021 Jun 2.
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 ((HO)-GCIB-SIMS) (at 1.6 μm beam spot size), followed by profiling cell-type specific lanthanide antibodies on the same tissue section using C-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.
肿瘤微环境（TME）中不同细胞的时空组织是理解它们复杂的通信网络和免疫景观的关键，这些免疫景观存在于受损组织中。对天然 TME 中相互作用的单细胞进行多组学分析，对于提供关于导致免疫抑制和肿瘤进展的重编程机制的进一步信息至关重要。这需要新技术来对同一组织样本中表型异质细胞进行生物分子分析。在这里，我们开发了一种新的方法，用于使用水气相团簇离子束二次离子质谱（(HO)-GCIB-SIMS）（在 1.6μm 束斑大小下）对冷冻水合组织切片上的单个细胞进行全面脂质组学和代谢组学分析，然后使用 C-SIMS（在 1.1μm 束斑大小下）对同一组织切片上的细胞类型特异性镧系元素抗体进行分析。我们揭示了不同类型的 TME 单个细胞中超过 150 种关键离子（例如脂质和重要代谢物）的分布和强度存在明显差异，例如活跃增殖的肿瘤细胞和浸润的免疫细胞。证明 SIMS 成像在单细胞水平上整合同一组织切片中的多组学分析的可行性，将为脂质重编程和代谢反应在各种组织微环境中正常调节或病理性细胞间相互作用失调中的作用提供新的见解。
