Spectral tracing of deuterium for imaging glucose metabolism

Spectral tracing of deuterium for imaging glucose metabolism
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DOI:
10.1038/s41551-019-0393-4
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发表时间:
2019-05-01
影响因子:
28.1
通讯作者:
Min, Wei
Min, Wei
中科院分区:
工程技术1区
文献类型:
--
作者:
Zhang, Luyuan;Shi, Lingyan;Min, Wei

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细胞和组织通常表现出明显的空间和动力学代谢异质性。常见的葡萄糖成像技术报告葡萄糖摄取或代谢活性,但不跟踪葡萄糖衍生的合成代谢产物的功能利用。在这里,我们报告的光学成像的显微镜技术,通过氘(STRIDE)的光谱跟踪,来自葡萄糖的各种大分子。基于受激拉曼散射成像,STRIDE通过从氘化葡萄糖前体转移的碳-氘键的富集和不同光谱,可视化新合成的大分子(例如DNA、蛋白质、脂质和糖原)的代谢动力学。STRIDE还可以使用来自不同葡萄糖同位素体的光谱差异,使用脉冲追踪协议来可视化时间上分离的葡萄糖群体。我们还表明,STRIDE可用于成像葡萄糖代谢在许多小鼠组织,包括肿瘤,脑,肠和肝脏,在10 mM的碳-氘键的检测限。STRIDE提供了葡萄糖合成代谢利用的高分辨率和化学信息评估。
Cells and tissues often display pronounced spatial and dynamical metabolic heterogeneity. Common glucose-imaging techniques report glucose uptake or catabolism activity, yet do not trace the functional utilization of glucose-derived anabolic products. Here we report a microscopy technique for the optical imaging, via the spectral tracing of deuterium (STRIDE), of diverse macromolecules derived from glucose. Based on stimulated Raman-scattering imaging, STRIDE visualizes the metabolic dynamics of newly synthesized macromolecules, such as DNA, protein, lipids and glycogen, via the enrichment and distinct spectra of carbon-deuterium bonds transferred from the deuterated glucose precursor. STRIDE can also use spectral differences derived from different glucose isotopologues to visualize temporally separated glucose populations using a pulse-chase protocol. We also show that STRIDE can be used to image glucose metabolism in many mouse tissues, including tumours, brain, intestine and liver, at a detection limit of 10 mM of carbon-deuterium bonds. STRIDE provides a high-resolution and chemically informative assessment of glucose anabolic utilization.