Centre for Inflammation ResearchThe Queen's Medical Research InstituteEdinburgh BioQuarterUniversity of EdinburghEdinburghUK.
MRC Human Genetics UnitInstitute of Genetics and CancerUniversity of EdinburghEdinburghUK.
Hepatology. 2022 Oct;76(4):1219-1230. doi: 10.1002/hep.32408. Epub 2022 Mar 6.
The concept of hepatocyte functional zonation is well established, with differences in metabolism and xenobiotic processing determined by multiple factors including oxygen and nutrient levels across the hepatic lobule. However, recent advances in single-cell genomics technologies, including single-cell and nuclei RNA sequencing, and the rapidly evolving fields of spatial transcriptomic and proteomic profiling have greatly increased our understanding of liver zonation. Here we discuss how these transformative experimental strategies are being leveraged to dissect liver zonation at unprecedented resolution and how this new information should facilitate the emergence of novel precision medicine-based therapies for patients with liver disease.
肝细胞功能分区的概念已经得到很好的确立,其代谢和外源物质处理的差异由多种因素决定,包括肝小叶内的氧和营养水平。然而,单细胞基因组学技术的最新进展,包括单细胞和细胞核 RNA 测序,以及空间转录组学和蛋白质组学分析领域的迅速发展,极大地提高了我们对肝脏分区的理解。在这里,我们讨论了这些变革性的实验策略如何以前所未有的分辨率来剖析肝脏分区,以及这些新信息应该如何促进基于新型精准医学的肝脏疾病治疗方法的出现。