A multiregional proteomic survey of the postnatal human brain
Open accessAbstract
Detailed observations of transcriptional, translational and post-translational events in the human brain are essential to improving our understanding of its development, function and vulnerability to disease. Here, we exploited label-free quantitative tandem mass-spectrometry to create an in-depth proteomic survey of regions of the postnatal human brain, ranging in age from early infancy to adulthood. Integration of protein data with existing matched whole-transcriptome sequencing (RNA-seq) from the BrainSpan project revealed varied patterns of protein-RNA relationships, with generally increased magnitudes of protein abundance differences between brain regions compared to RNA. Many of the differences amplified in protein data were reflective of cytoarchitectural and functional variation between brain regions. Comparing structurally similar cortical regions revealed significant differences in the abundances of receptor-associated and resident plasma membrane proteins that were not readily observed in the RNA expression data.
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Homeostatic processes can regulate the abundance of proteins, such that a raised level of a transcript does not always increase the abundance of the corresponding protein.
“Homeostatic processes can regulate the abundance of proteins, such that the raised level of a transcript does not always increase the abundance of the corresponding protein [8, 56, 59].”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [8]
The Results section on mRNA and protein abundance reports genes with regional RNA differences but no corresponding protein difference, supporting the claim that more transcript does not always mean more protein. The Discussion also says mRNA expression is an incomplete measure of protein abundance. Neither passage attributes this mismatch specifically to homeostatic processes; the paper discusses protein stability and localization instead. Page numbers were not supplied in our copy. (LLM, conf=0.86)
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- Authors
- Carlyle, B. C., Kitchen, R. R., Kanyo, J. E., Voss, E. Z., Pletikos, M., Sousa, A. M. M., Lam, T. T., Gerstein, M. B., Sestan, N., & Nairn, A. C.
- Affiliations
- Yale University (US)
- Corresponding author
- Nairn, Angus C.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2017-11-13
- Volume
- 20
- Issue
- 12
- Pages
- 1787-1795
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5894337
- OpenAlex
- W2767910296
- Cited by
- 143
- References
- 59
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 14 · 2023: 19 · 2022: 21 · 2021: 19 · 2020: 20 · 2019: 11 · 2018: 14
- FWCI
- 5.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1s10od019967-01, 5r01mh094714-04, 1s10od018034-01)
- National Institute on Aging (P50AG047270)
- National Institute of Mental Health (R01MH110926, U01MH103339, R01-MH094714, R21MH105881, U01MH103365, U01MH103340, R21MH102791, R01MH105472, P50MH106934, U01MH103392, R01MH105898, R21MH103877, U01MH103346)
- National Institute on Drug Abuse (P30DA018343)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- BrainSpan, label-free quantitative proteomics, membrane proteins, plasma membrane proteins, neocortex, brain development, brain aging, cytoarchitecture, cortical regions
- MeSH terms
- Adolescent, Adult, Aging, Animals, Animals, Newborn, Brain Chemistry, Child, Child, Preschool, Humans, Infant, Infant, Newborn, RNA, RNA, Messenger, Sequence Analysis, RNA, Peptide Library, Gene Expression Profiling, Proteomics, Mice, Tandem Mass Spectrometry, Young Adult, High-Throughput Nucleotide Sequencing, Transcriptome
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