Ablation of Foxl1-Cre-labeled hepatic progenitor cells and their descendants impairs recovery of mice from liver injury.
Ablation of Foxl1-Cre-labeled hepatic progenitor cells and their descendants impairs recovery of mice from liver injury.
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DOI：
10.1053/j.gastro.2014.09.039
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发表时间：
2015-01
期刊：
影响因子：
29.4
通讯作者：
Kaestner KH
中科院分区：
文献类型：
--
作者：
Shin S;Upadhyay N;Greenbaum LE;Kaestner KH
Foxl 1+肝祖细胞（HPC）在肝损伤后分化为胆管细胞和肝细胞。我们研究了Foxl 1 + HPC在小鼠肝损伤恢复中的需求。我们开发了小鼠，其中我们可以追踪和删除Foxl 1表达的HPC及其后代（Foxl 1-Cre;RosaYFP/iDTR小鼠）。Foxl 1-Cre阴性小鼠用作对照。通过将雄性小鼠置于胆碱缺乏、乙硫氨酸补充（CDE）的饮食中15天，诱导其肝损伤;然后将小鼠置于正常饮食中，并允许其恢复。通过将雌性小鼠置于含5-二乙氧羰基-1，4-二氢可力丁的饲料中诱导其肝损伤，随后是恢复期。在恢复期，对一些小鼠注射白喉毒素，以删除Foxl 1-Cre标记的HPC及其后代。从所有小鼠收集肝脏，并通过免疫荧光、定量逆转录PCR、流式细胞术和组织学分析进行分析。Foxl 1-Cre标记的HPC是CDE饮食诱导损伤后肝脏中胆管细胞和肝细胞发育所必需的。与YFP阴性肝细胞相比，YFP+肝细胞中含有氧化应激、DNA损伤或细胞死亡标志物的百分比较小，表明YFP+肝细胞是新形成的细胞。注射来自Foxl-Cre;RosaYFP/iDTR小鼠的白喉毒素缺失的YFP+细胞，并阻止肝脂肪变性的消退。在从含二氢可力丁的饮食诱导的损伤中恢复的小鼠中，大多数胆管细胞来自Foxl 1-Cre标记的HPC。删除YFP+细胞并没有改变肝损伤或肝功能标志物的水平。基于对Foxl 1-Cre;RosaYFP/iDTR小鼠的研究，在CDE饮食诱导的损伤后，肝脏中胆管细胞和肝细胞的发育需要Foxl 1 + HPC和/或其后代。
Foxl1+ hepatic progenitor cells (HPCs) differentiate into cholangiocytes and hepatocytes following liver injury. We investigated the requirement for Foxl1+ HPCs in recovery from liver injury in mice. We developed mice in which we can trace and delete Foxl1-expressing HPCs and their descendants (Foxl1-Cre;RosaYFP/iDTR mice). Foxl1-Cre-negative mice were used as controls. Liver damage was induced in male mice by placing them on choline-deficient, ethionine-supplemented (CDE) diets for 15 days; mice were then placed on normal diets and allowed to recover. Liver damage was induced in female mice by placing them on 5-diethoxycarbonyl-1,4-dihydrocollidine-containing diets, followed by a recovery period. Some mice were given injections of diphtheria toxin mice during the recovery phase, to delete Foxl1-Cre–marked HPCs and their descendants. Livers were collected from all mice and analyzed by immunofluorescence, quantitative reverse transcription PCR, flow cytometry, and histologic analyses. Foxl1-Cre-marked HPCs were required for development of cholangioctyes and hepatocytes in livers following CDE diet-induced injury. A smaller percentage of YFP+ hepatocytes contained markers of oxidative stress, DNA damage, or cell death than YFP-negative hepatocytes, indicating that YFP+ hepatocytes are newly formed cells. Injection of diphtheria toxin deleted YFP+ cells from Foxl1-Cre;RosaYFP/iDTR mice and prevented the resolution of hepatic steatosis. In mice recovering from dihydrocollidine-containing diet-induced injury, most cholangiocytes arose from Foxl1-Cre-marked HPCs. Deletion of YFP+ cells did not alter levels of markers of liver injury or liver function. Based on studies of Foxl1-Cre;RosaYFP/iDTR mice, Foxl1+ HPCs and/or their descendants are required for development of cholangioctyes and hepatocytes in liver following CDE diet-induced injury.
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影响因子：
13.5
作者：
Tarlow, Branden D.;Finegold, Milton J.;Grompe, Markus
通讯作者：
Grompe, Markus
DOI：
10.1038/labinvest.2009.6
发表时间：
2009-04
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
--
影响因子：
48
作者：
Buch, T;Heppner, FL;Waisman, A
通讯作者：
Waisman, A
影响因子：
13.5
作者：
Sackett, Sara D.;Li, Zhaodong;Hurtt, Reginald;Gao, Yan;Wells, Rebecca G.;Brondell, Karrie;Kaestner, Klaus H.;Greenbaum, Linda E.
通讯作者：
Greenbaum, Linda E.
辅助成人肝祖细胞的起源，生物学和治疗潜力。
影响因子：
--
作者：
Shin S;Kaestner KH
通讯作者：
Kaestner KH