Sharma Kirti, Schmitt Sebastian, Bergner Caroline G, Tyanova Stefka, Kannaiyan Nirmal, Manrique-Hoyos Natalia, Kongi Karina, Cantuti Ludovico, Hanisch Uwe-Karsten, Philips Mari-Anne, Rossner Moritz J, Mann Matthias, Simons Mikael
Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.
Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Nat Neurosci. 2015 Dec;18(12):1819-31. doi: 10.1038/nn.4160. Epub 2015 Nov 2.
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.
大脑转录组和连接组图谱正在生成，但目前在蛋白质组方面还缺乏同等的努力。我们进行了基于高分辨率质谱的蛋白质组学研究，以深入分析小鼠大脑及其主要脑区和细胞类型。将少突胶质细胞、星形胶质细胞、小胶质细胞和皮质神经元中鉴定出的12934种蛋白质与转录组的深度测序数据进行比较，表明蛋白质组得到了深度覆盖。细胞类型特异性蛋白质被定义为比平均表达量丰富十倍以上，约占蛋白质组的十分之一，其中细胞表面蛋白质的比例过高。为了证明我们资源的实用性，我们专注于这类蛋白质，并鉴定出IgLON家族的粘附分子Lsamp作为髓鞘形成的负调节因子。我们的研究结果为从系统层面理解中枢神经系统中的细胞类型多样性提供了一个框架，并为分析大脑发育和功能提供了丰富的资源。
