Zhou Tingting, Kiran Musunuru, Lui Kathy O, Ding Qiurong
CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Department of Medicine, and Department of Genetics, Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Life Med. 2022 Sep 29;1(3):333-344. doi: 10.1093/lifemedi/lnac040. eCollection 2022 Dec.
Liver fibrogenesis is a highly dynamic and complex process that drives the progression of chronic liver disease toward liver failure and end-stage liver diseases. Despite decades of intense studies, the cellular and molecular mechanisms underlying liver fibrogenesis remain elusive, and no approved therapies to treat liver fibrosis are currently available. The rapid development of single-cell RNA sequencing (scRNA-seq) technologies allows the characterization of cellular alterations under healthy and diseased conditions at an unprecedented resolution. In this Review, we discuss how the scRNA-seq studies are transforming our understanding of the regulatory mechanisms of liver fibrosis. We specifically emphasize discoveries on disease-relevant cell subpopulations, molecular events, and cell interactions on cell types including hepatocytes, liver sinusoidal endothelial cells, myofibroblasts, and macrophages. These discoveries have uncovered critical pathophysiological changes during liver fibrogenesis. Further efforts are urged to fully understand the functional contributions of these changes to liver fibrogenesis, and to translate the new knowledge into effective therapeutic approaches.
肝纤维化是一个高度动态且复杂的过程，它促使慢性肝病向肝衰竭和终末期肝病发展。尽管经过数十年的深入研究，肝纤维化背后的细胞和分子机制仍不清楚，目前尚无获批的治疗肝纤维化的疗法。单细胞RNA测序（scRNA-seq）技术的迅速发展使得以前所未有的分辨率表征健康和患病条件下的细胞变化成为可能。在本综述中，我们讨论了scRNA-seq研究如何改变我们对肝纤维化调节机制的理解。我们特别强调了在与疾病相关的细胞亚群、分子事件以及包括肝细胞、肝窦内皮细胞、肌成纤维细胞和巨噬细胞等细胞类型之间的细胞相互作用方面的发现。这些发现揭示了肝纤维化过程中关键的病理生理变化。迫切需要进一步努力，以充分了解这些变化对肝纤维化的功能贡献，并将新知识转化为有效的治疗方法。
