In a new international collaborative study, a comprehensive map of all proteins expressed in 17 regions of the human prefrontal cortex (PFC) has been launched based on RNA-seq gene expression profiling of 165 micro-dissected samples from both PFC and three reference cortices (frontal, parietal and temporal cortex), obtained from equal numbers of male and female donors, including both left and right hemispheres. The results are complemented with RNAscope and published single-cell transcriptomics data for the analysis of cellular localization. The human PFC controls many cognitive and other functions and has been associated with several mental and neurological disorders. Thus, our study provides new tools to neuroscience and medical research to help understand possible roles of a large number of proteins in different subregions of the PFC.
The study suggests that the well-established anatomical and functional heterogeneity of the human PFC is also reflected in the expression pattern of the neuropeptides. The closely located and functionally different PFC subregions are heterogenous with unique peptide/transmitter-related transcript profiles, including microcircuitries, involving local glutamatergic neurons co-expressing HCRT/ORX, galanin or OXT and respective receptors. The finding will contribute to the basic understanding of the PFC and facilitate efforts from academia and pharmaceutical companies to identify novel therapeutic strategies of relevance for human brain disorders.
The results have been published in the Proceedings of the National Academy of Sciences (PNAS) (https://www.pnas.org/doi/abs/10.1073/pnas.2123146119), all data is released in the Human Protein Atlas Brain section (www.proteinatlas.org/brain) and can be explored and downloaded for further analysis.
The project was a combined effort of Linköping University (Sweden), Karolinska Institutet, SciLifeLab, the KTH-Royal Institute of Technology, the Human Brain Tissue Bank (Hungary) and McGill University (Canada) with support from the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Hungarian Brain Research Program and the SciLifeLab & Wallenberg Data-Driven Life Science Program.
Human Protein Atlas
The Human Protein Atlas (HPA) is a program based at the Science for Life Laboratory (Stockholm) and started in 2003 with the aim to map all of the human proteins in cells, tissues and organs using integration of various omics technologies, including antibody-based imaging, mass spectrometry based proteomics, transcriptomics and systems biology. All the data in the knowledge resource is open access to allow scientists both in academia and industry to freely use the data for exploration of the human proteome. Version 21.1 consists of 10 separate sections, each focusing on a particular aspect of analysis of the human proteins, including one section on brain. The Human Protein Atlas program has already contributed to several thousands of publications in the field of human biology and disease and it has been selected by the organization ELIXIR (www.elixireurope.org) as a European core resource due to its fundamental importance for a wider life science community. The HPA consortium is funded by the Knut and Alice Wallenberg Foundation.For more information, see: www.proteinatlas.org
Semmelweis Human Brain Tissue Bank
The Human Brain Tissue Bank, Semmelweis University, Budapest (HBTB) is unique for two reasons:
1) It collects only microdissected human brain samples individually removed by the "micropunch technique" from 274 different brain areas or nuclei, and store them at -70oC. The Database of the HBTB contains medical, pathological and neuro-pathological reports on each of the diseased persons.
2) Samples are taken only from brains with short, 2-10 hours, post-mortem delay. The microdissected brain samples are available strictly for research studies in scientific collaborations.
