Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute, Rehovot, Israel.
Cell Stem Cell. 2022 Jun 2;29(6):973-989.e10. doi: 10.1016/j.stem.2022.04.008.
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 heterogeneity of 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, creating the mitotic pressure required to repopulate the necrotic pericentral zone rapidly. A subset of hepatocytes located at the regenerating front transiently upregulate fetal-specific genes, including Afp and Cdh17, as they reprogram to a pericentral state. Zonated endothelial, hepatic stellate cell (HSC), and macrophage populations are differentially involved in immune recruitment, proliferation, and matrix remodeling. We observe massive transient infiltration of myeloid cells, yet stability of lymphoid cell abundance, in accordance with a global decline in antigen presentation. Our study provides a resource for understanding the coordinated programs of zonal liver regeneration.
肝脏在急性区域性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，单细胞方法是研究这一过程的必要手段。 在这里，我们使用空间分辨的单细胞 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。我们发现肝细 胞在整个肝小叶中增殖，产生了快速重新填充坏死中央区所需的有丝 分裂压力。位于再生前缘的一组肝细胞短暂地上调了胎儿特异性基 因，包括 Afp 和 Cdh17，因为它们重新编程为中央区状态。分带的内皮细 胞、肝星状细胞 (HSC) 和巨噬细胞群体在免疫募集、增殖和基质重塑 方面的参与程度不同。我们观察到大量髓样细胞的短暂浸润，但淋 巴细胞数量的稳定性，与抗原呈递的整体下降一致。我们的研究为理 解区域性肝脏再生的协调程序提供了资源。
