Human-specific features and developmental dynamics of the brain N-glycome

• DOI: 10.1126/sciadv.adg2615
• Publication Date: 2023-12-06T18:59:41Z
• Authors: Thomas S. Klarić; Ivan Gudelj; Gabriel Santpere; Mislav Novokmet; Frano Vučković; Shaojie Ma; Hannah M. Doll; Ryan Risgaard; Shveta Bathla; Amir Karger; Angus C. Nairn; Victor Luria; Ivona Bečeheli; Chet C. Sherwood; John J. Ely; Patrick R. Hof; André M. M. Sousa; Djuro Josić; Gordan Lauc; Nenad Sestan
• Keywords: razvoj; Adult; 0301 basic medicine; Glycosylation; Mozak; N-glikom; post-translacijska modifikacija; Brain; N-glikozilacija; Mass Spectrometry; Rats; 03 medical and health sciences; Evolucija; glikani; Humans; Animals; Biomedicine and Life Sciences; Neurobiologia

Comparative “omics” studies have revealed unique aspects of human neurobiology, yet an evolutionary perspective of the brain N-glycome is lacking. We performed multiregional characterization of rat, macaque, chimpanzee, and human brain N-glycomes using chromatography and mass spectrometry and then integrated these data with complementary glycotranscriptomic data. We found that, in primates, the brain N-glycome has diverged more rapidly than the underlying transcriptomic framework, providing a means for rapidly generating additional interspecies diversity. Our data suggest that brain N-glycome evolution in hominids has been characterized by an overall increase in complexity coupled with a shift toward increased usage of α(2-6)–linked N -acetylneuraminic acid. Moreover, interspecies differences in the cell type expression pattern of key glycogenes were identified, including some human-specific differences, which may underpin this evolutionary divergence. Last, by comparing the prenatal and adult human brain N-glycomes, we uncovered region-specific neurodevelopmental pathways that lead to distinct spatial N-glycosylation profiles in the mature brain.