空间转录组学在肝病研究中的应用进展

doi:10.19586/j.2095-2341.2025.0017

生物技术进展 ›› 2025, Vol. 15 ›› Issue (4): 645-654.DOI: 10.19586/j.2095-2341.2025.0017

• 进展评述 • 上一篇

空间转录组学在肝病研究中的应用进展

万令飞(), 潘文婷, 雍雨婷, 李元帅, 赵悦, 阎新龙()

北京工业大学化学与生命科学学院，北京 100124

收稿日期:2025-02-14 接受日期:2025-03-31 出版日期:2025-07-25 发布日期:2025-09-08
通讯作者: 阎新龙
作者简介:万令飞 E-mail: wan-lingfei@outlook.com；
基金资助:
北京市自然科学基金和市教委基金联合基金重点项目(KZ202210005010)

Research Progress in Spatial Transcriptomics Technology for Liver Disease Research

Lingfei WAN(), Wenting PAN, Yuting YONG, Yuanshuai LI, yue ZHAO, Xinlong YAN()

College of Chemistry and Life Science，Beijing University of Technology，Beijing 100124，China

Received:2025-02-14 Accepted:2025-03-31 Online:2025-07-25 Published:2025-09-08
Contact: Xinlong YAN

摘要/Abstract

摘要：

肝脏疾病的发生和发展受到多种细胞类型及其空间组织方式的精细调控。空间转录组学（spatial transcriptomics，ST）可在组织切片水平实现基因表达的空间定位，目前已成为解析肝脏疾病微环境动态变化的重要技术。综述总结了ST技术在酒精性脂肪性肝病、肝纤维化及肝细胞癌等多种肝脏疾病中的研究进展，梳理了其在揭示组织空间异质性、细胞间互作及动态变化方面的应用，并分析了当前技术面临的瓶颈和未来发展方向，以期为肝病早期诊断的生物标志物筛选、靶向治疗方案设计以及个性化医疗策略制定提供数据基础和理论支撑。

关键词: 空间转录组, 肝病研究, 肝细胞癌, 肝纤维化, 精准医学

Abstract:

The occurrence and development of liver diseases are finely regulated by various cell types and their spatial organization patterns. Spatial transcriptomics （ST） can achieve spatial localization of gene expression at the tissue slice level and has become an important technique for analyzing liver tissue to reveal dynamic changes in the disease microenvironment. The review summarized the research progress of ST technology in various liver diseases， such as alcoholic fatty liver disease， liver fibrosis， and hepatocellular carcinoma， sorted out the applications in revealing tissue spatial heterogeneity， intercellular interactions， and dynamic changes， and analyzed the current bottlenecks and future development directions of the technology. The aim is to provide data foundation and theoretical support for biomarker discovery， targeted therapeutic design，and personalized treatment strategies for early diagnosis and intervention of liver diseases.

Key words: spatial transcriptomics, liver disease research, hepatocellular carcinoma, liver fibrosis, precision medicine

中图分类号:

Q291

万令飞, 潘文婷, 雍雨婷, 李元帅, 赵悦, 阎新龙. 空间转录组学在肝病研究中的应用进展[J]. 生物技术进展, 2025, 15(4): 645-654.

Lingfei WAN, Wenting PAN, Yuting YONG, Yuanshuai LI, yue ZHAO, Xinlong YAN. Research Progress in Spatial Transcriptomics Technology for Liver Disease Research[J]. Current Biotechnology, 2025, 15(4): 645-654.

图/表 6

参考文献 47

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技术平台	分类	分辨率	检测区域	适用场景	优势	局限性
10×Genomics Visium	测序型	~55 µm	6.5×6.5 mm²	组织大范围基因表达分析，适用于肝脏、肿瘤、神经组织	成熟商业化平台，实验流程标准化，支持FFPE样本	分辨率较低，每个点包含多个细胞，难以解析单细胞信息
Slide-seq^[5]	测序型	~10 µm	6.2×6.2 mm²	适用于神经系统、肝小叶分区研究	分辨率高于Visium，支持全转录组测序	捕获面积受限，微珠随机分布可能影响数据一致性
Stereo-seq	测序型	~500 nm	最大可达13.2 cm²	适用于超高分辨率组织解析，如胚胎发育、肿瘤	分辨率极高，可进行亚细胞级别分析，适用于大组织	数据处理复杂，计算量大，对实验条件要求高
MERFISH	成像型	~100 nm	1~2 mm²	适用于单细胞/亚细胞级别的基因表达研究，如神经科学、胚胎发育	超高分辨率，可检测10 000+目标基因	仅能检测预设基因，实验流程复杂，数据分析要求高
SeqFISH	成像型	~100 nm	1~2 mm²	适用于亚细胞级别的RNA成像，如免疫组织分析	高通量，可检测10 000+目标基因	仅适用于已知基因组，无法进行全转录组分析
STARmap^[6]	成像型	~200 nm	1~3 mm²	适用于单细胞分辨率的组织分析，如大脑结构	结合水凝胶扩增，提高信噪比，适合深层组织	基因检测数量有限，实验复杂度高

技术平台	分类	分辨率	检测区域	适用场景	优势	局限性
10×Genomics Visium	测序型	~55 µm	6.5×6.5 mm²	组织大范围基因表达分析，适用于肝脏、肿瘤、神经组织	成熟商业化平台，实验流程标准化，支持FFPE样本	分辨率较低，每个点包含多个细胞，难以解析单细胞信息
Slide-seq^[5]	测序型	~10 µm	6.2×6.2 mm²	适用于神经系统、肝小叶分区研究	分辨率高于Visium，支持全转录组测序	捕获面积受限，微珠随机分布可能影响数据一致性
Stereo-seq	测序型	~500 nm	最大可达13.2 cm²	适用于超高分辨率组织解析，如胚胎发育、肿瘤	分辨率极高，可进行亚细胞级别分析，适用于大组织	数据处理复杂，计算量大，对实验条件要求高
MERFISH	成像型	~100 nm	1~2 mm²	适用于单细胞/亚细胞级别的基因表达研究，如神经科学、胚胎发育	超高分辨率，可检测10 000+目标基因	仅能检测预设基因，实验流程复杂，数据分析要求高
SeqFISH	成像型	~100 nm	1~2 mm²	适用于亚细胞级别的RNA成像，如免疫组织分析	高通量，可检测10 000+目标基因	仅适用于已知基因组，无法进行全转录组分析
STARmap^[6]	成像型	~200 nm	1~3 mm²	适用于单细胞分辨率的组织分析，如大脑结构	结合水凝胶扩增，提高信噪比，适合深层组织	基因检测数量有限，实验复杂度高

空间转录组学在肝病研究中的应用进展

Research Progress in Spatial Transcriptomics Technology for Liver Disease Research

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