以色列魏茨曼科学研究所Shalev Itzkovitz课题组揭示急性损伤后区域性肝再生的时空程序。该研究于2022年6月2日发表于国际一流学术期刊《细胞—干细胞》。

研究人员使用了空间分辨率的单细胞RNA测序（scRNA-seq）来研究急性对乙酰氨基酚（APAP）中毒后小鼠肝脏再生的动态变化。研究人员发现，肝细胞在整个肝小叶增殖，产生了快速重新填充坏死中心区所需的有丝分裂压力。位于再生前线的肝细胞亚群在重新规划为中心区状态时，会暂时上调胎儿特异性基因，包括Afp和Cdh17。内皮细胞、肝星状细胞（HSC）和巨噬细胞群体不同程度地参与了免疫招募、增殖和基质重塑。

研究人员观察到骨髓细胞的大量瞬时浸润，但淋巴细胞的丰度却很稳定，这与抗原呈现的全面下降相一致。这项研究为了解区域性肝脏再生的协调程序提供了一个资源。

据介绍，肝脏在急性区域损伤后具有快速再生的显著能力。鉴于肝细胞类型的空间异质性，单细胞方法对于研究这一过程是必要的。

附：英文原文

Title: The spatiotemporal program of zonal liver regeneration following acute injury

Author: Shani Ben-Moshe, Tamar Veg, Rita Manco, Stav Dan, Delfina Papinutti, Aviezer Lifshitz, Aleksandra A. Kolodziejczyk, Keren Bahar Halpern, Eran Elinav, Shalev Itzkovitz

Issue&Volume: 2022/06/02

Abstract: The liver carries a remarkable ability to regenerate rapidly after acute zonal damage.Single-cell approaches are necessary to study this process, given the spatial heterogeneityof liver cell types. Here, we use spatially resolved single-cell RNA sequencing (scRNA-seq)to study the dynamics of mouse liver regeneration after acute acetaminophen (APAP)intoxication. We find that hepatocytes proliferate throughout the liver lobule, creatingthe mitotic pressure required to repopulate the necrotic pericentral zone rapidly.A subset of hepatocytes located at the regenerating front transiently upregulate fetal-specificgenes, including Afp and Cdh17, as they reprogram to a pericentral state. Zonatedendothelial, hepatic stellate cell (HSC), and macrophage populations are differentiallyinvolved in immune recruitment, proliferation, and matrix remodeling. We observe massivetransient infiltration of myeloid cells, yet stability of lymphoid cell abundance,in accordance with a global decline in antigen presentation. Our study provides aresource for understanding the coordinated programs of zonal liver regeneration.

DOI: 10.1016/j.stem.2022.04.008

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00161-8