The spatiotemporal program of zonal liver regeneration following acute injury
The spatiotemporal program of zonal liver regeneration following acute injury
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DOI：
10.1016/j.stem.2022.04.008
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发表时间：
2022-06-02
期刊：
影响因子：
23.9
通讯作者：
Itzkovitz, Shalev
中科院分区：
文献类型：
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作者：
Ben-Moshe, Shani;Veg, Tamar;Itzkovitz, Shalev
肝脏具有在急性带状损伤后迅速再生的非凡能力。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。在这里，我们使用空间分辨单细胞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力学。我们发现肝细胞在整个肝小叶中增殖，产生快速填充坏死中心周围区域所需的有丝分裂压力。位于再生前沿的一组肝细胞在重新编程到中心周围状态时，瞬时上调胎儿特有的基因，包括AFP和CDH17。带状内皮细胞、肝星状细胞(HSC)和巨噬细胞群体在免疫募集、增殖和基质重塑中有不同的作用。我们观察到大量的一过性髓系细胞渗透，但淋巴细胞丰度稳定，与全球抗原呈递的下降相一致。我们的研究为了解区域肝再生的协调方案提供了资源。
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.