Ning Meng, Lu Donghui, Liang Dong, Ren Pei-Gen
Department of Endocrinology, Peking University Shenzhen Hospital, Shenzhen, China.
Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Front Mol Biosci. 2025 Mar 25;12:1513993. doi: 10.3389/fmolb.2025.1513993. eCollection 2025.
Developing drugs for the treatment of Metabolic Associated Steatohepatitis (MASH) has always been a significant challenge. Researchers have been dedicated to exploring drugs and therapeutic strategies to alleviate disease progression, but treatments remain limited. This is partly due to the complexity of the pathophysiological processes, and inadequate knowledge of the cellular and molecular mechanisms in MASH. Especially, the liver non-parenchymal cells (NPCs) like Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells which play critical roles in live function, immune responses, fibrosis and disease progression. Deciphering how these cells function in MASH, would help understand the pathophysiological processes and find potential drug targets. In recent years, new technologies have been developed for single-cell transcriptomic sequencing, making cell-specific transcriptome profiling a reality in healthy and diseased livers. In this review, we discussed how the use of single-cell transcriptomic sequencing provided us with an in-depth understanding of the heterogeneous, cellular interactions among non-parenchymal cells and tried to highlight recent discoveries in MASH by this technology. It is hoped that the summarized features and markers of various subclusters in this review could provide a technical reference for further experiments and a theoretical basis for clinical applications.
开发用于治疗代谢相关脂肪性肝炎(MASH)的药物一直是一项重大挑战。研究人员一直致力于探索药物和治疗策略以缓解疾病进展,但治疗方法仍然有限。部分原因在于病理生理过程的复杂性,以及对MASH中细胞和分子机制的了解不足。特别是,肝非实质细胞(NPCs),如库普弗细胞、肝星状细胞和窦状内皮细胞,它们在肝脏功能、免疫反应、纤维化和疾病进展中发挥着关键作用。弄清楚这些细胞在MASH中的功能,将有助于理解病理生理过程并找到潜在的药物靶点。近年来,已开发出用于单细胞转录组测序的新技术,使得在健康和患病肝脏中进行细胞特异性转录组分析成为现实。在这篇综述中,我们讨论了单细胞转录组测序的应用如何使我们深入了解非实质细胞之间的异质性和细胞相互作用,并试图突出通过该技术在MASH方面的最新发现。希望本综述中总结的各种亚群的特征和标志物能够为进一步的实验提供技术参考,并为临床应用提供理论依据。