Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma

Jiajun Du; Lu Wei

doi:10.1117/12.2576833

5 March 2021 Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma

Jiajun Du, Lu Wei

Proceedings Volume 11656, Advanced Chemical Microscopy for Life Science and Translational Medicine 2021; 116561G (2021) https://doi.org/10.1117/12.2576833
Event: SPIE BiOS, 2021, Online Only

Abstract

We utilized Raman spectro-microscopy to non-invasively probe metabomics within single live cells, aiming to identify druggable metabolic susceptibilities from a series of patient-derived BRAF mutant melanoma cell lines. Each cell line represents a phenotype with different characteristic level of de-differentiation and BRAFi (BRAF inhibitor) resistance. First, with single-cell Raman spectroscopy and stimulated Raman scattering (SRS) microscopy, followed by transcriptomics analysis, we identified lipid processes as major metabolic functional difference between different phenotypes. We then utilized hyperspectral-SRS imaging on intracellular single organelles to identify a previously unknown susceptibility of lipid desaturation within de-differentiated cell lines. Drugging this target leads to cellular apoptosis accompanied by phase separated intracellular domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests highly heterogenous metabolic responses and possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies.

Conference Presentation

Citation Download Citation

Jiajun Du and Lu Wei "Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma", Proc. SPIE 11656, Advanced Chemical Microscopy for Life Science and Translational Medicine 2021, 116561G (5 March 2021); https://doi.org/10.1117/12.2576833

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