Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells.
IF: 17.694
Cited by: 69


Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid mono-unsaturation within de-differentiated mesenchymal cells with innate resistance to BRAF inhibition. Drugging this target leads to cellular apoptosis accompanied by the formation of phase-separated intracellular membrane domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies.


Spatial Metabolomics

MeSH terms

Cell Line, Tumor
Fatty Acids
Lipid Droplets
Lipid Metabolism
Oleic Acid
Spectrum Analysis, Raman
Stearoyl-CoA Desaturase


Du, Jiajun
Su, Yapeng
Qian, Chenxi
Yuan, Dan
Miao, Kun
Lee, Dongkwan
Ng, Alphonsus H C
Wijker, Reto S
Ribas, Antoni
Levine, Raphael D
Heath, James R
Wei, Lu

Recommend literature

Similar data