The adult liver has exceptional ability to regenerate, but how it sustains normal metabolic activities during regeneration remains unclear. Here, we use partial hepatectomy (PHx) in tandem with single-cell transcriptomics to track cellular transitions and heterogeneities of ~22,000 liver cells through the initiation, progression, and termination phases of mouse liver regeneration. Our results reveal that following PHx, a subset of hepatocytes transiently reactivates an early-postnatal-like gene expression program to proliferate, while a distinct population of metabolically hyperactive cells appears to compensate for any temporary deficits in liver function. Importantly, through combined analysis of gene regulatory networks and cell-cell interaction maps, we find that regenerating hepatocytes redeploy key developmental gene regulons, which are guided by extensive ligand-receptor mediated signaling events between hepatocytes and non-parenchymal cells. Altogether, our study offers a detailed blueprint of the intercellular crosstalk and cellular reprogramming that balances the metabolic and proliferation requirements of a regenerating liver.

中文翻译：

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细胞可塑性平衡了再生肝脏的代谢和增殖动力学

成年肝脏具有异常的再生能力，但在再生过程中如何维持正常的代谢活动仍不清楚。在这里，我们将部分肝切除术（PHx）与单细胞转录组学串联使用，以追踪小鼠肝再生的起始，进展和终止阶段的细胞迁移和约22,000个肝细胞的异质性。我们的研究结果表明，继PHx之后，肝细胞的一个子集会暂时重新激活早期产后样基因表达程序以增殖，而代谢异常活跃细胞的独特群体似乎可以弥补肝功能的任何暂时性缺陷。重要的是，通过对基因调控网络和细胞间相互作用图谱的综合分析，我们发现再生的肝细胞重新部署了关键的发育基因调控因子，它们由肝细胞与非实质细胞之间广泛的配体-受体介导的信号传导事件指导。总之，我们的研究提供了细胞间串扰和细胞重编程的详细蓝图，可以平衡再生肝脏的代谢和增殖需求。