دورية أكاديمية
Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells
| العنوان: | Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells |
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| المؤلفون: | 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 |
| المصدر: | Nature Communications, 11, Art. No. 4830, (2020-09-24) |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2020 |
| المجموعة: | Caltech Authors (California Institute of Technology) |
| مصطلحات موضوعية: | Cancer metabolism, Cellular imaging, Lipids, Raman spectroscopy, Target identification |
| الوصف: | 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. ; © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://github.com/mesako/Melanoma-PublicationTest; https://resolver.caltech.edu/CaltechAUTHORS:20201221-101511711Test; https://doi.org/10.1038/s41467-020-18376-xTest; oai:authors.library.caltech.edu:n0npk-4qf04; https://www.ncbi.nlm.nih.gov/pmc/PMC7518429Test; eprintid:105516; resolverid:CaltechAUTHORS:20200924-122708002 |
| DOI: | 10.1038/s41467-020-18376-x |
| الإتاحة: | https://doi.org/10.1038/s41467-020-18376-xTest https://www.ncbi.nlm.nih.gov/pmc/PMC7518429Test |
| حقوق: | info:eu-repo/semantics/openAccess ; Other |
| رقم الانضمام: | edsbas.9C9400A2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-020-18376-x |
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