Fast Metabolic Glycan Labeling for Click-Labeling and Imaging of Sialoglycans in Living Acute Brain Slices from Mice and Human Patients

Autor: Xia, Xiaoqian, Sun, De-en, Tang, Qi, Liu, Xianyu, Fan, Xinqi, Wan, Yi, Cui, Shiyong, Zhang, Xu, Liu, Qingzhu, Jiang, Yuwu, Wu, Ye, Cheng, Bo, Chen, Xing
Zdroj: Journal of the American Chemical Society; August 2024, Vol. 146 Issue: 31 p22008-22016, 9p
Abstrakt: Living acute brain slices provide a practical platform for imaging sialylation in human brain pathology. However, the limited lifespan of acute brain slices has impeded the use of metabolic glycan labeling (MGL), which requires long-term incubation of clickable unnatural sugars such as N-azidoacetylmannosamine (ManNAz) to metabolically incorporate azides into sialoglycans. Here, we report a fast variant of MGL (fMGL), in which ManNAz-6-phosphate enables efficient azidosugar incorporation within 12 h by bypassing the bottleneck step in the sialic acid biosynthesis pathway, followed by click-labeling with fluorophores and imaging of sialoglycans in acute brain slices from mice and human patients. In the clinical samples of ganglioglioma, fMGL-based imaging reveals specific upregulation of sialylation in astrocyte-like but not neuron-like tumor cells. In addition, fMGL is integrated with click-expansion microscopy for high-resolution imaging of sialoglycans in brain slices. The fMGL strategy should find broad applications in the tissue imaging of glycans and surgical pathology.
Databáze: Supplemental Index