TY - JOUR TI - Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells AU - Du, Jiajun AU - Su, Yapeng AU - Qian, Chenxi AU - Yuan, Dan AU - Miao, Kun AU - Lee, Dongkwan AU - Ng, Alphonsus H. C. AU - Wijker, Reto S. AU - Ribas, Antoni AU - Levine, Raphael D. AU - Heath, James R. AU - Wei, Lu T2 - Nature Communications AB - 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. DA - 2020/09/24/ PY - 2020 DO - 10.1038/s41467-020-18376-x DP - www.nature.com VL - 11 IS - 1 SP - 4830 LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-020-18376-x Y2 - 2020/09/24/16:13:23 ER -