Epigenetic regulation of neural N-glycomics

Glycan expression is tightly regulated in a cell-type-specific manner, which is essential for the diverse functions of glycans. In particular, neural cells such as neurons and astrocytes are known to express unique functional glycans not found in other cells, and these glycans play critical roles in high-order brain functions and various neurological disorders. However, little is known about how the expression of these neural glycans is established and maintained. Here, we investigated which glycans are expressed in each primary neural cell and how epigenetics contributes to the expression of neural glycans. We first isolated primary neurons, astrocytes, and fibroblasts from mouse embryos and carried out N-glycomic and glycosyltransferase (GlycoT)-transcriptomic analyses to identify N-glycans specific to a particular neural cell type and to clarify the underlying transcriptional basis. We next treated the cells with epigenetic drugs (5-aza-2'-deoxycytidine (5-aza) and trichostatin A (TSA)) and characterized the changes in GlycoT-transcriptomes and N-glycomes. We found that the N-glycomes in neurons were highly stable and resistant to epigenetic stimulation. In contrast, astrocytes showed dynamic N-glycan changes after treatment, such as a shift in the linkages of sialic acid. These results provide novel insights into how the expression of neural glycans is maintained and epigenetically regulated.