第三军医大学蔡晋团队取得一项新突破。他们提出了人类代谢功能障碍相关脂肪变性肝病的空间分解多组学研究。这一研究成果于2025年11月24日发表在国际顶尖学术期刊《自然—遗传学》上。

该课题组研究人员生成了61个人类肝脏的单细胞和空间转录组学和代谢组学图谱，包括对照组(n=10)，代谢功能障碍相关脂肪变性肝（MASL） (n=17)和代谢功能障碍相关脂肪性肝炎（MASH） （n = 34）。研究人员确定了小眼相关转录因子（MITF）是脂质相关巨噬细胞（LAMs）处理脂质能力的关键调节因子，并进一步揭示了LAMs通过肝细胞生长因子分泌介导的肝保护作用。无偏倚的空间转录组反褶积描绘了在晚期MASH中丰富的纤维化相关基因程序，表明纤维化区域内中央静脉内皮细胞和肝星状细胞之间存在纤维化串扰。基于质谱成像的空间代谢组学证明了MASLD特异性磷脂积累，可能与脂蛋白相关磷脂酶A2介导的LAMs磷脂代谢有关。这个空间分辨的人类MASLD多组学图谱，可以在人类MASLD空间多组学图谱上查询，为其机制和治疗研究提供了有价值的依据。

据了解，代谢功能障碍相关脂肪变性肝病（MASLD）是世界范围内慢性肝病的主要疾病。

附：英文原文

Title: Spatially resolved multi-omics of human metabolic dysfunction-associated steatotic liver disease

Author: Li, Ziyu, Luo, Gang, Gan, Changpei, Zhang, Huayu, Li, Ling, Zhang, Xiaoxun, Xing, Xudong, Hu, Simeng, Tan, Xu, Ding, Jingjing, Zhang, Liangjun, Peng, Ying, Xu, Ziqian, Pan, Qiong, Byrne, Christopher D., Targher, Giovanni, Jin, Xiao-Zhi, Xie, Wei, Ouyang, Xinshou, Zheng, Ming-Hua, Bai, Fan, Chai, Jin

Issue&Volume: 2025-11-24

Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide. We generated single-cell and spatial transcriptomic and metabolomic maps from 61 human livers, including controls (n=10), metabolic dysfunction-associated steatotic liver (MASL) (n=17) and metabolic dysfunction-associated steatohepatitis (MASH) (n=34). We identified microphthalmia-associated transcription factor (MITF) as a key regulator of the lipid-handling capacity of lipid-associated macrophages (LAMs), and further revealed a hepato-protective role of LAMs mediated through hepatocyte growth factor secretion. Unbiased deconvolution of spatial transcriptomics delineated a fibrosis-associated gene program enriched in advanced MASH, suggesting profibrotic crosstalk between central vein endothelial and hepatic stellate cells within fibrotic regions. Mass spectrometry imaging-based spatial metabolomics demonstrated MASLD-specific accumulation of phospholipids, potentially linked to lipoprotein-associated phospholipase A2-mediated phospholipid metabolism in LAMs. This spatially resolved multi-omics atlas of human MASLD, which can be queried at the Human Masld Spatial Multiomics Atlas, provides a valuable resource for mechanistic and therapeutic studies.

DOI: 10.1038/s41588-025-02407-8

Source: https://www.nature.com/articles/s41588-025-02407-8