A High-Resolution N-Glycoproteome Atlas Reveals Tissue-Specific Glycan Remodeling but Non-random Structural Microheterogeneities

The mouse is a widely used model organism in biomedical research, yet a comprehensive understanding of its tissue-specific glycoproteome has been limited due to the structural complexity and microheterogeneity of glycans. Here, we present the most extensive high-resolution N-glycoproteomic atlas across 24 mouse tissues, which comprises of 3,045 N-glycans with distinct structures attached at 8,681 glycosites on 74,277 glycopeptides and 5,026 glycoproteins. Overall glycan structural patterns show enormous tissue-specific diversities, acting as superior molecular signatures of tissue identity and system origins. Notably, even commonly expressed glycoproteins undergo tissue-dependent glycan remodeling, suggesting that glycosylation may fine-tune protein functions to meet specialized biological demands. These patterns are further shaped by subcellular localization, which constrains glycan variabilities across compartments. Co-occurrence network analyses also expose substructural biases and non-random microheterogeneities among glycans attached at the same glycosites. The dataset serves as a valuable database resource for advancing the structural and functional understanding of glycoproteins.