编辑丨王多鱼 排版丨水成文 染色体外 DNA （extrachromosomal DNA，ecDNA） 是一种独立于染色体存在的环状 DNA 分子，在 30%-50% 的恶性肿瘤患者中被检测到。尽管早在 1965 年研究人员就在神经母细胞瘤中观察到其存在 （当 时称为双微体） ，但受限于技术手段，其存在的生物学意义长期未被阐明。 近年来的研究发现，ecDNA 可携带完整的致癌基因 （例如 MYC、EGFR） 及其增强子序列。当这些基因从 染色体脱落并环化形成 ecDNA 后，原本的表观遗传修饰 （例如 DNA 甲基化和组蛋白修饰） 记忆丢失，导 致癌基因的异常激活。 临床证据表明，携带 ecDNA 的肿瘤患者往往表现出更高的恶性程度、更强的治疗抵抗和更差的临床预后。 因此，靶向 ecDNA 的抗肿瘤策略 （例如干扰其复制与维持、调控表观遗传重塑） 具有重要治疗潜力。然 而，ecDNA 的复制与维持机制、表观遗传重塑及其在肿瘤发生发展中的精确作用，仍是当前研究的核心挑 战。解决这些问题将为开发新型抗癌疗法提供关键突破口。 2025 年 4 月 28 日，中国科学院深圳先进技术研究院定量合成生物学全国重点实验室、 ...

Core Viewpoint - The research team from Shanghai has published the world's first high-precision complete 3D liver atlas, providing a revolutionary research tool for addressing chronic liver diseases such as hepatic fibrosis [3][6]. Group 1: Research Significance - The study addresses a significant public health challenge, with over 200 million patients suffering from fatty liver disease in China and more than one million deaths annually due to liver cirrhosis globally [3][4]. - The high-precision 3D liver atlas allows for a comprehensive understanding of liver anatomy and pathology, which was previously limited to 2D imaging techniques [3][4]. Group 2: Technological Innovation - The research utilized the MOST (Microscopic Optical Sectioning Tomography) technology to achieve ultra-high resolution 3D imaging of the liver at 0.35×0.35×2 micrometers, effectively creating a "digital twin" of the liver [4][6]. - This technology captures critical spatial relationships among liver structures, including the liver lobes, bile ducts, and blood vessels, and reveals fine structures like peribiliary microvascular networks that traditional methods could not observe [4][6]. Group 3: Findings and Applications - The study established a pathological atlas of liver fibrosis using a carbon tetrachloride (CCl4) induced mouse model, revealing a correlation between the severity of hepatocyte steatosis and proximity to the central vein [6][7]. - The application of deep learning techniques enabled automatic segmentation and analysis of large-scale 3D pathological data, identifying that the volume proportion of steatotic hepatocytes in fibrotic livers reached 30.76% [6][7]. - The findings provide new insights into the pathogenesis of liver fibrosis and potential targets for targeted therapy, enhancing the efficiency and accuracy of pathological analysis [6][7]. Group 4: Future Implications - The established technological framework is not only applicable for basic research but also offers new approaches for clinical diagnosis and treatment of liver diseases [7]. - The successful application of high-precision liver atlas construction and 3D pathological analysis techniques is expected to be further promoted in the research and clinical pathology of other liver diseases, supporting the development of more effective treatment strategies [7].