鼠肝细胞类型分辨定量蛋白质组学。

Cell-type-resolved quantitative proteomics of murine liver.

机构信息

Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.

出版信息

Cell Metab. 2014 Dec 2;20(6):1076-87. doi: 10.1016/j.cmet.2014.11.002.

DOI:10.1016/j.cmet.2014.11.002

PMID:25470552

Abstract

Mass spectrometry (MS)-based proteomics provides a powerful approach to globally investigate the biological function of individual cell types in mammalian organs. Here, we applied this technology to the in-depth analysis of purified hepatic cell types from mouse. We quantified 11,520 proteins, making this the most comprehensive proteomic resource of any organ to date. Global protein copy number determination demonstrated that a large proportion of the hepatocyte proteome is dedicated to fatty acid and xenobiotic metabolism. We identified as-yet-unknown components of the TGF-β signaling pathway and extracellular matrix in hepatic stellate cells, uncovering their regulative role in liver physiology. Moreover, our high-resolution proteomic data set enabled us to compare the distinct functional roles of hepatic cell types in cholesterol flux, cellular trafficking, and growth factor receptor signaling. This study provides a comprehensive resource for liver biology and biomedicine.

摘要

基于质谱（MS）的蛋白质组学提供了一种强大的方法，可以全局研究哺乳动物器官中单个细胞类型的生物学功能。在这里，我们将这项技术应用于从小鼠中纯化的肝细胞类型的深入分析。我们定量了 11520 种蛋白质，这是迄今为止任何器官中最全面的蛋白质组学资源。全球蛋白质拷贝数测定表明，肝细胞蛋白质组的很大一部分专门用于脂肪酸和异生物质代谢。我们鉴定了肝星状细胞中 TGF-β信号通路和细胞外基质的未知成分，揭示了它们在肝脏生理学中的调节作用。此外，我们的高分辨率蛋白质组数据集使我们能够比较肝实质细胞类型在胆固醇通量、细胞运输和生长因子受体信号转导中的不同功能作用。这项研究为肝脏生物学和生物医学提供了一个全面的资源。