Klarić, Thomas S.Gudelj, IvanSantpere Baró, Gabriel, 1981-Novokmet, MislavVučković, FranoMa, ShaojieDoll, HannahRisgaard, RyanBathla, ShvetaKarger, AmirNairn, Angus C.Luria, VictorBečeheli, IvonaSherwood, Chet C.Ely, John J.Hof, Patrick R.Sousa, André M. M.Josić, DjuroLauc, GordanSestan, Nenad2024-11-082024-11-082023Klarić 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: 10.1101/2023.01.11.5235252375-2548http://hdl.handle.net/10230/68466Comparative “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.application/pdfeng© 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.Neurobiologiainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1101/2023.01.11.523525info:eu-repo/semantics/openAccess