Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells.
Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells.
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DOI：
10.1038/s41467-020-18376-x
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发表时间：
2020-09-24
影响因子：
16.6
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Du J;Su Y;Qian C;Yuan D;Miao K;Lee D;Ng AHC;Wijker RS;Ribas A;Levine RD;Heath JR;Wei L
非侵入性探测单个活细胞内的代谢物是高度期望的，但具有挑战性。在这里，我们利用拉曼光谱显微镜的单细胞内的代谢物的空间映射，从一系列的患者来源的黑色素瘤细胞系的具体目标，确定药物代谢的可药用性。每种细胞系代表癌细胞去分化的不同特征水平。首先，用拉曼光谱，然后用受激拉曼散射（SRS）显微镜和转录组学分析，我们确定了脂肪酸合成途径作为分化的黑素细胞的药物敏感性。然后，我们利用细胞内脂滴的高光谱-SRS成像来鉴定具有对BRAF抑制的先天抗性的去分化间充质细胞内的脂质单不饱和的先前未知的易感性。给药该靶点导致细胞凋亡，伴随着相分离的细胞内膜结构域的形成。亚细胞拉曼光谱显微镜与脂质组学和转录组学的整合表明了这种药理学治疗的潜在脂质调节机制。我们的方法应该提供一个空间分辨的单细胞代谢组学研究的一般方法。单细胞代谢组学可以深入了解伴随疾病状态的代谢重编程。在这里，作者使用拉曼光谱显微镜进行非侵入性代谢物分析和鉴定单活黑色素瘤细胞中的药物代谢敏感性。
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. Single-cell metabolomics can offer deep insights into the metabolic reprogramming that accompanies disease states. Here, the authors use Raman spectro-microscopy for non-invasive metabolite analysis and identification of druggable metabolic susceptibilities in single live melanoma cells.
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影响因子：
64.5
作者：
Hugo W;Shi H;Sun L;Piva M;Song C;Kong X;Moriceau G;Hong A;Dahlman KB;Johnson DB;Sosman JA;Ribas A;Lo RS
通讯作者：
Lo RS
影响因子：
64.5
作者：
Hauser AS;Chavali S;Masuho I;Jahn LJ;Martemyanov KA;Gloriam DE;Babu MM
通讯作者：
Babu MM
影响因子：
12.3
作者：
Budnik B;Levy E;Harmange G;Slavov N
通讯作者：
Slavov N
影响因子：
8.8
作者：
Delgado-Goni, Teresa;Galobart, Teresa Casals;Beloueche-Babari, Mounia
通讯作者：
Beloueche-Babari, Mounia
影响因子：
3.3
作者：
Fu, Dan;Holtom, Gary;Freudiger, Christian;Zhang, Xu;Xie, Xiaoliang Sunney
通讯作者：
Xie, Xiaoliang Sunney