Regio-specific glycan expression within the mammalian brain and tumors

The mammalian brain exhibits a complex glycan code that orchestrates neural connectivity, yet the spatial organization of functionally critical modifications of glycoproteins, such as fucosylation and sialylation, remains unclear. Using novel monoclonal antibodies (mAbs) designed for glycan detection, we mapped expression of glycan epitopes with unprecedented sensitivity, revealing non-overlapping expression patterns. Combined with targeted N-/O-glycan profiling, we found that expression of fucosylated and sialylated glycans occurs in anatomically distinct domains in both murine and human central nervous system (CNS). Key findings include fucosylated O-glycans marking brain endothelial cells, sialylated O-glycans decorating lecticans at the nodes of Ranvier, whereas the accessory olfactory bulb harbors unique fucosylated N-glycans. RNAseq and co-localization studies confirm regio-specific glycosyltransferase activity driving this partitioning. We also found that brain tumors are distinguished by upregulated expression of specific fucosylated/sialylated epitopes compared to normal tissue. The mAb-based approach uncovers regio-specific glycan expression with implications for neurodevelopment and cancer diagnostics.