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Nat Neurosci. 2015 Dec;18(12):1819-31. doi: 10.1038/nn.4160. Epub 2015 Nov 2.

Cell type- and brain region-resolved mouse brain proteome.

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Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.
Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Department of Neurology, University of Göttingen, Göttingen, Germany.
Department of Psychiatry, Ludwig-Maximillian University, Munich, Germany.
Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Estonia.
Department of Neuropathology, University of Göttingen, Göttingen, Germany.


Brain transcriptome and connectome maps are being generated, but an equivalent effort on the proteome is currently lacking. We performed high-resolution mass spectrometry-based proteomics for in-depth analysis of the mouse brain and its major brain regions and cell types. Comparisons of the 12,934 identified proteins in oligodendrocytes, astrocytes, microglia and cortical neurons with deep sequencing data of the transcriptome indicated deep coverage of the proteome. Cell type-specific proteins defined as tenfold more abundant than average expression represented about a tenth of the proteome, with an overrepresentation of cell surface proteins. To demonstrate the utility of our resource, we focused on this class of proteins and identified Lsamp, an adhesion molecule of the IgLON family, as a negative regulator of myelination. Our findings provide a framework for a system-level understanding of cell-type diversity in the CNS and serves as a rich resource for analyses of brain development and function.

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