Contributions of new hepatocyte lineages to liver growth, maintenance, and regeneration in mice.

Contributions of new hepatocyte lineages to liver growth, maintenance, and regeneration in mice.
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新的肝细胞谱系对小鼠肝脏生长,维持和再生的贡献。

DOI:
10.1002/hep.24398
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发表时间:
2011-08
期刊:
影响因子:
13.5
通讯作者:
Schmidt, Edward E.
Schmidt, Edward E.
中科院分区:
医学1区
文献类型:
--
作者:
Iverson, Sonya V.;Comstock, Kristin M.;Kundert, Jean A.;Schmidt, Edward E.

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新肝细胞谱系的从头分化对正常肝脏生理学的贡献尚不清楚。在此,使用了一种在血清白蛋白基因启动子/增强子驱动的 Cre 转基因 (albCre) 初次激活后的有限时间内对细胞进行独特标记的系统,用于研究小鼠中从未接触过 Alb 的前体的新肝细胞谱系的出生率。使用双色荧光标记基因测量经过的时间,该基因在暴露于 Cre 后从表达 tdTomato(tdT,红色荧光)转换为表达 GFP(绿色荧光)。 GFP 的积累和 tdT 的衰减均导致规则的荧光跃迁,并在体内进行了校准。在正常成年人中,该系统显示,在过去四天内,0.076% 的稳态水平的肝细胞已从以前从未表达过 albCre 的细胞谱系中分化出来。与静息的成年肝脏相比,这些新生肝细胞的相对丰度在幼年正常生长的肝脏中升高了3.7倍,在正常成人部分肝切除后的肝脏再生过程中升高了8.6倍。由 Alb 幼稚细胞产生的新生肝细胞谱系有助于正常条件下的肝脏维持。肝细胞谱系的出生率可能因肝脏的生理状态而异。
The contributions that de novo differentiation of new hepatocyte lineages makes to normal liver physiology are unknown. Here a system that uniquely marks cells during a finite period following primary activation of a serum albumin gene promoter/enhancer-driven Cre transgene (albCre) was used to investigate birthrates of new hepatocyte lineages from Alb-naïve precursors in mice. Elapsed time was measured using a two-color fluorescent marker-gene that converts from expressing tdTomato (tdT, red-fluorescent) to expressing GFP (green-fluorescent) upon exposure to Cre. Accumulation of GFP and decay of tdT each contributed to a regular fluorescence transition, which was calibrated in vivo. In normal adults, this system revealed that a steady-state level of 0.076% hepatocytes had differentiated within the previous four days from cell lineages that had never previously expressed albCre. As compared to resting adult livers, the relative abundance of these newborn hepatocytes was elevated 3.7-fold in normal growing livers of juveniles and 8.6-fold during liver regeneration following partial hepatectomy in normal adults. Newborn hepatocyte lineages arising from Alb-naïve cells contribute to liver maintenance under normal conditions. Hepatocyte lineage birthrates can vary in response to the liver’s physiological status.
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期刊: CARCINOGENESIS
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