Cell type– and brain region–resolved mouse brain proteome

The authors performed a comprehensive proteome analysis of the adult mouse brain, its major regions and CNS cell types at a depth of >13,000 proteins. This new resource represents the largest collection of cell type–resolved protein expression data of the brain. The power of the data set was illustrated by identifying novel adhesion molecules in glia and neuron interaction. 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.