Self-renewing diploid Axin2(+) cells fuel homeostatic renewal of the liver.
Self-renewing diploid Axin2(+) cells fuel homeostatic renewal of the liver.
复制标题
DOI：
10.1038/nature14863
复制
发表时间：
2015-08-13
期刊：
影响因子：
64.8
通讯作者：
Nusse R
中科院分区：
文献类型：
--
作者：
Wang B;Zhao L;Fish M;Logan CY;Nusse R
未受伤肝脏中新肝细胞的来源仍然是一个悬而未决的问题。通过使用 Wnt 响应基因 Axin2 进行谱系追踪，我们识别出肝小叶中央静脉附近的一群增殖和自我更新的细胞。这些中央周围细胞表达早期肝脏祖细胞标记物Tbx3，是二倍体，因此不同于成熟肝细胞，成熟肝细胞大多是多倍体。中央周围细胞的后代分化为Tbx3阴性的多倍体肝细胞，并且可以在稳态更新期间替代肝小叶上的所有肝细胞。邻近的中央静脉内皮细胞提供维持中央周围细胞的Wnt信号，从而构成生态位。因此，我们鉴定了肝脏中促进肝细胞稳态更新的细胞群，描述了其解剖学生态位，并鉴定了调节其活性的分子信号。
The source of new hepatocytes in the uninjured liver has remained an open question. By lineage tracing using the Wnt-responsive gene Axin2, we identify a population of proliferating and self-renewing cells adjacent to the central vein in the liver lobule. These pericentral cells express the early liver progenitor marker Tbx3, are diploid, and thus differ from mature hepatocytes, which are mostly polyploid. The descendants of pericentral cells differentiate into Tbx3-negative, polyploid hepatocytes and can replace all hepatocytes along the liver lobule during homeostatic renewal. Adjacent central vein endothelial cells provide Wnt signals that maintain the pericentral cells, thereby constituting the niche. Thus, we identify a cell population in the liver that subserves homeostatic hepatocyte renewal, characterize its anatomical niche, and identify molecular signals that regulate its activity.