Using mass spectrometry imaging to map fluxes quantitatively in the tumor ecosystem.
Using mass spectrometry imaging to map fluxes quantitatively in the tumor ecosystem.
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DOI：
10.1038/s41467-023-38403-x
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发表时间：
2023-05-19
影响因子：
16.6
通讯作者：
Patti, Gary J.
中科院分区：
文献类型：
--
作者：
Schwaiger-Haber, Michaela;Stancliffe, Ethan;Anbukumar, Dhanalakshmi S.;Sells, Blake;Yi, Jia;Cho, Kevin;Adkins-Travis, Kayla;Chheda, Milan G.;Shriver, Leah P.;Patti, Gary J.
肿瘤由跨越不同微环境的多种细胞类型组成。质谱成像（MSI）有可能识别肿瘤生态系统和周围组织中的代谢模式，但传统的工作流程尚未完全整合代谢组学实验技术的广度。在这里，我们结合联合收割机MSI，稳定同位素标记，和同位素光谱分析的空间变异映射分布的代谢物丰度，营养成分，代谢周转通量在小鼠的大脑窝藏GL 261胶质瘤，广泛使用的模型胶质母细胞瘤。当与MSI整合时，离子迁移率、解吸电喷雾电离和基质辅助激光解吸电离的组合揭示了多种合成代谢途径的改变。相对于周围健康组织，胶质瘤中的从头脂肪酸合成通量增加约3倍。脂肪酸延伸通量相对于周围健康组织升高甚至更高8倍，并突出了延伸酶活性在胶质瘤中的重要性。同位素谱分析最初被设计用于评估来自批量样品的代谢通量。在这里，作者采用这种方法来推断通过使用质谱成像从组织中的离散区域的通量，显示小鼠脑肿瘤中脂肪酸合成通量增加。
Tumors are comprised of a multitude of cell types spanning different microenvironments. Mass spectrometry imaging (MSI) has the potential to identify metabolic patterns within the tumor ecosystem and surrounding tissues, but conventional workflows have not yet fully integrated the breadth of experimental techniques in metabolomics. Here, we combine MSI, stable isotope labeling, and a spatial variant of Isotopologue Spectral Analysis to map distributions of metabolite abundances, nutrient contributions, and metabolic turnover fluxes across the brains of mice harboring GL261 glioma, a widely used model for glioblastoma. When integrated with MSI, the combination of ion mobility, desorption electrospray ionization, and matrix assisted laser desorption ionization reveals alterations in multiple anabolic pathways. De novo fatty acid synthesis flux is increased by approximately 3-fold in glioma relative to surrounding healthy tissue. Fatty acid elongation flux is elevated even higher at 8-fold relative to surrounding healthy tissue and highlights the importance of elongase activity in glioma. Isotopologue spectral analysis was originally designed to assess metabolic fluxes from bulk samples. Here, the authors adapted this approach to infer fluxes from discrete regions in tissue by using mass spectrometry imaging, showing increased fatty acid synthesis flux in brain tumors of mice.
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影响因子：
5.7
作者：
Kuemmerle NB;Rysman E;Lombardo PS;Flanagan AJ;Lipe BC;Wells WA;Pettus JR;Froehlich HM;Memoli VA;Morganelli PM;Swinnen JV;Timmerman LA;Chaychi L;Fricano CJ;Eisenberg BL;Coleman WB;Kinlaw WB
通讯作者：
Kinlaw WB
影响因子：
8.8
作者：
Gelman SJ;Naser F;Mahieu NG;McKenzie LD;Dunn GP;Chheda MG;Patti GJ
通讯作者：
Patti GJ
影响因子：
1.1
作者：
Davis ME
通讯作者：
Davis ME
影响因子：
4.3
作者：
通讯作者：
--
影响因子：
4.7
作者：
He, Michelle Junyi;Pu, Wenjun;Wang, Xi;Zhang, Wei;Tang, Donge;Dai, Yong
通讯作者：
Dai, Yong