Hepatocyte proliferation is the principal mechanism for generating new hepatocytes in liver homeostasis and regeneration. Recent studies have suggested that this ability is not equally distributed among hepatocytes but concentrated in a small subset of hepatocytes acting like stem cells, located around the central vein or distributed throughout the liver lobule and exhibiting active WNT signaling or high telomerase activity, respectively. These findings were obtained by utilizing components of these growth regulators as markers for genetic lineage tracing. Here, we used random lineage tracing to localize and quantify clonal expansion of hepatocytes in normal and injured liver. We found that modest proliferation of hepatocytes distributed throughout the lobule maintains the hepatocyte mass and that most hepatocytes proliferate to regenerate it, with diploidy providing a growth advantage over polyploidy. These results show that the ability to proliferate is broadly distributed among hepatocytes rather than limited to a rare stem cell-like population.

中文翻译：

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肝脏稳态和再生中肝细胞增殖的广泛分布。

肝细胞增殖是在肝脏稳态和再生中产生新肝细胞的主要机制。最近的研究表明，这种能力在肝细胞中分布不均，而是集中在一小部分肝细胞中，其作用类似于干细胞，位于中央静脉周围或分布在整个肝小叶中，分别表现出活跃的 WNT 信号传导或高端粒酶活性。这些发现是通过利用这些生长调节剂的成分作为遗传谱系追踪标记获得的。在这里，我们使用随机谱系追踪来定位和量化正常和受损肝脏中肝细胞的克隆扩增。我们发现分布在整个小叶中的肝细胞适度增殖维持了肝细胞质量，并且大多数肝细胞增殖以使其再生，二倍体比多倍体具有生长优势。这些结果表明，增殖能力广泛分布于肝细胞，而不是局限于罕见的干细胞样群体。