Broad Distribution of Hepatocyte Proliferation in Liver Homeostasis and Regeneration.
Broad Distribution of Hepatocyte Proliferation in Liver Homeostasis and Regeneration.
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DOI：
10.1016/j.stem.2019.11.001
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发表时间：
2020-01-02
期刊：
影响因子：
23.9
通讯作者：
Willenbring H
中科院分区：
文献类型：
--
作者：
Chen F;Jimenez RJ;Sharma K;Luu HY;Hsu BY;Ravindranathan A;Stohr BA;Willenbring H
肝细胞增殖是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匀，而是集中在一小部分肝细胞中，这些肝细胞像干细胞一样，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组分作为遗传谱系追踪的标记物而获得的。在这里，我们使用随机谱系追踪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，分布在整个小叶的肝细胞的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，二倍体提供了超过多倍性的生长优势。这些结果表明，增殖能力广泛分布在肝细胞中，而不限于罕见的干细胞样群体。Chen等人研究了肝小叶不同区域中肝细胞对正常和损伤肝脏中肝细胞替代的贡献程度的潜在差异。他们发现，原则上，肝细胞增殖的位置和程度是广泛分布的，损伤类型和倍性具有特定的影响。
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. Chen et al. investigate potential differences in how much hepatocytes in the different zones of the liver lobule contribute to hepatocyte replacement in normal and injured liver. They find that, in principle, location and extent of hepatocyte proliferation are broadly distributed, with specific effects of type of injury and ploidy.
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