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

Klaric, T. S.; Gudelj, I.; Santpere, G.; Sousa, A. M. M.; Novokmet, M.; Vuckovic, F.; Ma, S.; Beceheli, I.; Sherwood, C. C.; Ely, J. J.; Hof, P. R.; Josic, D.; Lauc, G.; Sestan, N.

doi:10.1101/2023.01.11.523525

bioRxiv · 10.1101/2023.01.11.523525

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

Klaric, T. S.·Gudelj, I.·Santpere, G.·Sousa, A. M. M.·Novokmet, M.·Vuckovic, F.·Ma, S.·Beceheli, I.·Sherwood, C. C.·Ely, J. J.·Hof, P. R.·Josic, D.·Lauc, G.·Sestan, N.

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Abstract

Comparative "omics" studies have revealed unique aspects of human neurobiology, yet an evolutionary perspective of the brain N-glycome is lacking. Here, we performed multi-regional characterization of rat, macaque, chimpanzee, and human brain N-glycomes using chromatography and mass spectrometry, then integrated these data with complementary glycotranscriptomic data. We found that in primates the brain N-glycome has evolved more rapidly than the underlying transcriptomic framework, providing a mechanism for generating additional diversity. We show that brain N-glycome evolution in hominids has been characterized by an increase in complexity and (2-6)-linked N-acetylneuraminic acid along with human-specific cell-type expression of key glycogenes. Finally, by comparing the prenatal and adult human brain N-glycome, we identify region-specific neurodevelopmental pathways that lead to distinct spatial N-glycosylation profiles in the mature brain. One-Sentence SummaryEvolution of the human brain N-glycome has been marked by an increase in complexity and a shift in sialic acid linkage.

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Klaric, T. S., Gudelj, I., Santpere, G., Sousa, A. M. M., Novokmet, M., Vuckovic, F., Ma, S., Beceheli, I., Sherwood, C. C., Ely, J. J., Hof, P. R., Josic, D., Lauc, G., Sestan, N.. 2023-01-11. Human-specific features and developmental dynamics of the brain N-glycome. https://doi.org/10.1101/2023.01.11.523525

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