State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center of Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
J Proteome Res. 2022 Aug 5;21(8):1916-1929. doi: 10.1021/acs.jproteome.2c00190. Epub 2022 Jul 12.
The liver plays a unique role as a metabolic center of the body, and also performs other important functions such as detoxification and immune response. Here, we establish a cell type-resolved healthy human liver proteome including hepatocytes (HCs), hepatic stellate cells (HSCs), Kupffer cells (KCs), and liver sinusoidal endothelial cells (LSECs) by high-resolution mass spectrometry. Overall, we quantify total 8354 proteins for four cell types and over 6000 proteins for each cell type. Analysis of this data set and regulatory pathway reveals the cellular labor division in the human liver follows the pattern that parenchymal cells make the main components of pathways, but nonparenchymal cells trigger these pathways. Human liver cells show some novel molecular features: HCs maintain KCs and LSECs homeostasis by producing cholesterol and ketone bodies; HSCs participate in xenobiotics metabolism as an agent deliverer; KCs and LSECs mediate immune response through MHC class II-TLRs and MHC class I-TGFβ cascade, respectively; and KCs play a central role in diurnal rhythms regulation through sensing diurnal IGF and temperature flux. Together, this work expands our understandings of liver physiology and provides a useful resource for future analyses of normal and diseased livers.
肝脏作为身体的代谢中心发挥着独特的作用，同时还具有解毒和免疫反应等其他重要功能。在这里，我们通过高分辨率质谱法建立了一个包括肝细胞（HCs）、肝星状细胞（HSCs）、库普弗细胞（KCs）和肝窦内皮细胞（LSECs）在内的细胞类型解析的健康人类肝脏蛋白质组。总体而言，我们对四种细胞类型共定量了 8354 种蛋白质，对每种细胞类型定量了超过 6000 种蛋白质。对该数据集的分析和调控途径揭示了人类肝脏的细胞分工遵循这样的模式：实质细胞构成途径的主要成分，但非实质细胞触发这些途径。人类肝脏细胞显示出一些新的分子特征：HCs 通过产生胆固醇和酮体来维持 KCs 和 LSECs 的稳态；HSCs 作为一种药物输送者参与外源性物质代谢；KCs 和 LSECs 通过 MHC II-TLRs 和 MHC I-TGFβ级联反应分别介导免疫反应；KCs 通过感知昼夜 IGF 和温度通量在昼夜节律调节中发挥核心作用。总之，这项工作扩展了我们对肝脏生理学的理解，并为未来对正常和患病肝脏的分析提供了有用的资源。
