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

Klarić, Thomas S.; Gudelj, Ivan; Santpere Baró, Gabriel, 1981-; Novokmet, Mislav; Vučković, Frano; Ma, Shaojie; Doll, Hannah; Risgaard, Ryan; Bathla, Shveta; Karger, Amir; Nairn, Angus C.; Luria, Victor; Bečeheli, Ivona; Sherwood, Chet C.; Ely, John J.; Hof, Patrick R.; Sousa, André M. M.; Josić, Djuro; Lauc, Gordan; Sestan, Nenad

doi:http://dx.doi.org/10.1101/2023.01.11.523525

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

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Citació

Klarić TS, Gudelj I, Santpere G, Novokmet M, Vučković F, Ma S, et al. Human-specific features and developmental dynamics of the brain N-glycome. Science Advances. 2023;9(49):eadg2615. DOI: 10.1101/2023.01.11.523525

Resum

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.