活体捐献者的健康人类肝脏的空间图谱，这一成果由魏茨曼科学研究所Shalev Itzkovitz团队经过不懈努力而取得。2026年4月15日出版的《自然》发表了这项成果。

研究利用空间转录组学（Visium、Visium HD3、多路错误荧光原位杂交（MERFISH）和PhenoCycler成像）和单核RNA测序，团队分析了16个肝脏样本：8个来自年轻健康供体，8个来自肝脏病变个体，取样“邻近正常”组织。与肝脏病理个体的邻近正常组织相比，来自健康活体供体的肝脏显示出显著的基因表达差异。与小鼠和其他哺乳动物相比，肝细胞和非实质细胞沿肝小叶的门-中轴线表现出明显的分带性，其关键功能在中心周围转移。他们的图谱确定了早期脂肪变性肝细胞的动态程序，包括核编码线粒体蛋白的下降和线粒体编码转录物的代偿性增加。该研究为健康人类肝脏提供了空间基因表达参考，并对早期脂肪变性肝细胞的变化有了新的认识。

据悉，人体组织基因表达图谱的重建是具有挑战性的，因为从活的个体获得健康样本的机会有限。神经系统死亡的供体通常表现为缺血改变，病变区域附近的组织可能有基因表达改变。肝脏具有独特的再生能力，可以对健康的活体供体进行分析。

附：英文原文

Title: A spatial atlas of the healthy human liver from live donors

Author: Yakubovsky, Oran, Bahar Halpern, Keren, Shir, Sapir, Novoselsky, Roy, Afriat, Amichay, Egozi, Adi, Barkai, Tal, Harnik, Yotam, Hoefflin, Rouven, Korem Kohanim, Yael, Golani, Ofra, Goliand, Inna, Addadi, Yoseph, Kedmi, Merav, Keren-Shaul, Hadas, Fellus-Alyagor, Liat, Prichislov, Lena, Hirsch, Dana, Mayer, Chen, Pery, Ron, Pencovich, Niv, Taner, Timucin, Nachmany, Ido, Itzkovitz, Shalev

Issue&Volume: 2026-04-15

Abstract: Reconstructing gene expression atlases for human tissues is challenging due to limited access to healthy samples from live individuals. Neurologically deceased donors often show ischaemic changes, and tissues near diseased regions may have altered gene expression1,2. The liver, with its unique regenerative capacity, allows analysis from live healthy donors. Here, using spatial transcriptomics (Visium, Visium HD3, multiplexed error-robust fluorescence in situ hybridization (MERFISH)4 and PhenoCycler imaging5) and single-nucleus RNA sequencing6, we analysed 16 liver samples: 8 from young live healthy donors and 8 from individuals with liver pathology, sampling ‘adjacent normal’ tissue. Livers from live healthy donors displayed significant gene expression differences compared with the adjacent normal tissues from individuals with liver pathology. Hepatocytes and non-parenchymal cells exhibited marked zonation along the porto–central axis of the liver lobules, with key functions being pericentrally shifted compared to mice and other mammals. Our atlas identified dynamic programmes in early steatotic hepatocytes, including a decline in nuclear-encoded mitochondrial proteins and a compensatory increase in mitochondria-encoded transcripts. This study presents a spatial gene expression reference for the healthy human liver and insights into hepatocyte changes in early steatosis.

DOI: 10.1038/s41586-026-10377-y

Source: https://www.nature.com/articles/s41586-026-10377-y