Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Contributed by Hee-Sup Shin, October 5, 2020 (sent for review July 9, 2020; reviewed by Carlito B. Lebrilla, David M. Lubman, Alcino J. Silva, and Jeongmin Song)
Significance
Deciphering molecular mechanisms at the glycome level in mammalian brain remains a missing piece of the puzzle in molecular neuroscience due to the intrinsic complexity of glycosylation and the lack of analytical tools. Here, we uncovered the variation and diversity of glycome expression in human and mouse brain samples according to spatial and temporal differences. We further constructed a comprehensive synthesis map using glycans structurally elucidated by LC-MS/MS and found strong evidence on the conservation and developmental divergence of human and mouse prefrontal cortex N-glycome. Our data could be the reference for future mammalian brain glycome study. Furthermore, it provides valuable information on human brain glycome, which has languished in relative obscurity.
Abstract
Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale “omics” studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties. Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development. We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse. Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse. We found that glycan expression profiles were dynamically regulated during postnatal developments. A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified. Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development. Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development. Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
Footnotes
↵1H.-S.S. and H.J.A. contributed equally to this work.
- ↵2To whom correspondence may be addressed. Email: shin{at}ibs.re.kr or hjan{at}cnu.ac.kr.
Author contributions: M.J.W., C.S.W., R.G., S.B., H.-S.S., and H.J.A. designed research; J.L., S.H., M.K., S.-W.K., J.Y., S.O., H.H., I.J.J., D.Y., M.J.W., C.S.W., J.-H.K., J.S.Y., R.G., and S.B. performed research; J.L. and H.J.A. analyzed data; and J.L., H.-S.S., and H.J.A. wrote the paper.
Reviewers: C.B.L., University of California, Davis; D.M.L., University of Michigan; A.J.S., University of California, Los Angeles; and J.S., Cornell University.
Competing interest statement: H.J.A. and Carlito B. Lebrilla are coauthors on a 2019 method article.
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This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2014207117/-/DCSupplemental.
Data Availability.
All study data are included in the article and SI Appendix .
Published under the PNAS license.
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Spatial and temporal diversity of glycome expression in mammalian brain
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- Biochemistry
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