Physiological liver cell replacement is central to maintaining the organ's high metabolic activity, although its characteristics are difficult to study in humans. Using retrospective 14C birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, maintaining the liver a young organ (average age < 3 years). Hepatocyte renewal is highly dependent on the ploidy level. Diploid hepatocytes show an seven-fold higher annual exchange rate than polyploid hepatocytes. These observations support the view that physiological liver cell renewal in humans is mainly dependent on diploid hepatocytes, whereas polyploid cells are compromised in their ability to divide. Moreover, cellular transitions between these two subpopulations are limited, with minimal contribution to the respective other ploidy class under homeostatic conditions. With these findings, we present a new integrated model of homeostatic liver cell generation in humans that provides fundamental insights into liver cell turnover dynamics.

中文翻译：

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二倍体肝细胞驱动成年人的生理性肝更新

生理性肝细胞置换对于维持器官的高代谢活性至关重要，尽管其特性很难在人体中研究。使用细胞的回顾性14C出生日期，我们报告人肝细胞显示出连续且终生的更新，维持肝脏年轻的器官（平均年龄<3岁）。肝细胞更新高度依赖于倍性水平。二倍体肝细胞的年交换率比多倍体肝细胞高七倍。这些观察结果支持这样的观点，即人类的生理肝细胞更新主要取决于二倍体肝细胞，而多倍体细胞的分裂能力受到损害。而且，这两个亚群之间的细胞迁移受到限制，在稳态条件下对各个其他倍性的贡献最小。有了这些发现，我们提出了人类体内稳态肝细胞生成的新集成模型，该模型提供了对肝细胞更新动态的基本见解。