Summary: An international research team has published a comprehensive, open-access protein atlas of the mammalian brain, providing a high-resolution resource for studying protein expression across brain regions and species.
Source: Karolinska Institute
An international group of scientists led by Karolinska Institutet researchers has released a detailed map of proteins expressed in the brain. Published in Science, the open-access Brain Atlas gives researchers a powerful new resource to advance neurobiology and support development of improved diagnostics and treatments for neurological and psychiatric disorders.
The Brain Atlas is based on analysis of nearly 1,900 brain samples representing 27 distinct brain regions. It integrates human data with corresponding datasets from pig and mouse, enabling cross-species comparisons of protein expression. This resource is part of the Human Protein Atlas (HPA) program, hosted at the Science for Life Laboratory (SciLifeLab) in Sweden, and was produced in collaboration with partners in China (BGI) and Aarhus University in Denmark.
The study confirms that many core elements of brain organization are conserved across mammals, yet it also reveals notable species differences. These differences are especially prominent among components of neurotransmitter systems — in particular, receptors and neuropeptide-related proteins show divergent expression patterns between humans and mice. Such distinctions emphasize caution when using mouse models to represent human brain function in studies and drug development.
One of the most striking regional findings is the distinct molecular signature of the cerebellum. The cerebellum shows elevated expression of many proteins, including several that have been linked to psychiatric conditions, reinforcing the idea that this structure contributes to emotional processing in addition to motor control.
Researchers also observed that specific brain cell types share specialized proteins with peripheral organs. For example, astrocytes — glial cells that regulate the brain’s extracellular environment — express many transporters and metabolic enzymes similar to those found in liver cells. Likewise, microglial gene expression parallels immune cell signatures, suggesting functional overlap between brain immune cells and peripheral immune systems.
In addition to bulk tissue profiling, the Brain Atlas provides detailed visualizations for selected genes and proteins. These include high-resolution microscopic images showing protein distribution in human brain tissue and interactive, zoomable maps of protein localization in the mouse brain. The integration of multiple data types — transcriptomics, single-cell genomics, in situ hybridization, and antibody-based protein mapping — delivers a multilevel, genome-wide view of protein-coding genes across the mammalian brain.
The Human Protein Atlas initiative, launched in 2003, aims to map all human proteins across cells, tissues, and organs. All data in the HPA Brain Atlas are openly available, enabling researchers in academia and industry to freely explore protein expression patterns and to integrate these data into their own studies.
Key implications:
- Conserved regional organization across human, pig, and mouse brains supports shared mammalian brain architecture.
- Substantial species differences in neurotransmitter receptors and other signaling components caution against assuming direct equivalence between mouse and human brain biology for therapeutic research.
- The pig shows closer global expression profiles to human for several regions, such as cerebellum and hypothalamus, suggesting pigs may be preferable models for some studies.
- Many genes considered cell-type signatures in the brain are also highly expressed in peripheral organs, revealing shared molecular functions across tissues.
- The cerebellum exhibits a unique molecular profile, including genes implicated in neuropsychiatric disorders.
Funding: The research received major support from the Knut and Alice Wallenberg Foundation.
The full Brain Atlas is available through the Human Protein Atlas: proteinatlas.org/brain (open-access resource).
Source:
Karolinska Institute
Media Contacts:
Press Office – Karolinska Institute
Image Source:
The image is in the public domain.
Original Research: Closed access
“An atlas of the protein-coding genes in the human, pig and mouse brain”. Authors include Evelina Sjöstedt, Wen Zhong, Linn Fagerberg, Max Karlsson, Nicholas Mitsios, Csaba Adori, Per Oksvold, Fredrik Edfors, Agnieszka Limiszewska, Feria Hikmet, Jinrong Huang, Yutao Du, Lin Lin, Zhanying Dong, Ling Yang, Xin Liu, Hui Jiang, Xun Xu, Jian Wang, Huanming Yang, Lars Bolund, Adil Mardinoglu, Cheng Zhang, Kalle von Feilitzen, Cecilia Lindskog, Fredrik Pontén, Yonglun Luo, Tomas Hökfelt, Mathias Uhlén, and Jan Mulder. Science, DOI: 10.1126/science.aay5947.
Abstract (condensed)
The study presents a brain-centered knowledge resource that reports regional RNA and protein expression of all protein-coding genes in human, pig, and mouse brains. By combining transcriptomics and antibody-based mapping with other high-resolution methods, the project identifies regionally enriched genes, evaluates cell-type specificity, and compares brain expression profiles across species and against other human tissues. The integrated dataset supports cell-topology analyses, systems modeling, and exploration of genes linked to brain function and disease, providing an open-access platform for continued neuroscience research.