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Abstract
Glycosylation is cell and tissue-type specific, regulated throughout cellular differentiation. Glycoproteins and glycolipids adorn the surface of cells where they mediate cell-cell and cell-environment interactions and have known roles in adhesion, migration, and signaling events that are essential for normal tissue development. Defects of glycosylation, as seen in Congenital Disorders of Glycosylation, often results in severe developmental and intellectual disabilities. The role of glycosylation in other neurodevelopmental disorders such as Autism spectrum disorders has not been well explored. Characterizing the dynamics of cell-specific glycosylation patterns during human development provides a framework for understanding the pathophysiologic relevance of altered glycosylation in human diseases. Human pluripotent stem cells are a powerful tool that can be used to generate different human cell types and tissues. Human embryonic stem cells differentiated into multiple cell were used to study the regulation of glycosylation in human cellular development. Combined analysis of transcriptomes and glycomes of these cells revealed shifts in biosynthetic pathways between pluripotent, multipotent, and differentiated cells leading to the generation of glycan structural profiles unique to the different cell types. This data indicates a significant role for the regulation of glycan structures in development. In neural cultures generated from induced pluripotent stems cells of an Autism Spectrum Disorder patient with a mutation in synaptic adhesion gene NLGN4x, glycan profiles were altered and dysfunction in early neural development was evident. Investigation of these ASD patient cells reveals an undescribed early role for NLGN4 in neural development and provides a platform for studying the role of glycosylation in the poorly understood neurodevelopmental disorder of Autism.