Foxl1 is a marker of bipotential hepatic progenitor cells in mice.
Foxl1 is a marker of bipotential hepatic progenitor cells in mice.
复制标题
DOI：
10.1002/hep.22705
复制
发表时间：
2009-03
期刊：
影响因子：
13.5
通讯作者：
Greenbaum, Linda E.
中科院分区：
文献类型：
--
作者：
Sackett, Sara D.;Li, Zhaodong;Hurtt, Reginald;Gao, Yan;Wells, Rebecca G.;Brondell, Karrie;Kaestner, Klaus H.;Greenbaum, Linda E.
肝脏含有一群小的双电位兼性祖细胞，当成熟的肝细胞和/或胆管细胞不能增殖时，它们可以重建肝功能。间充质标志物，包括叉头转录因子基因家族的成员，已经在肝祖细胞中检测到。螺旋翼转录因子Foxl1定位于肠间充质细胞；但其在肝脏中的表达尚未见报道。我们发现Foxl1在正常肝脏的罕见细胞中表达，但在接受胆管结扎或喂食含ddc或CDE饮食的小鼠肝脏中被显著诱导。此外，我们使用Foxl1-Cre转基因小鼠与Rosa26R lacZ报告系杂交进行遗传谱系追踪，以证明Foxl1-Cre表达细胞在损伤后不久存在于门静脉周围区域。这些细胞产生肝细胞（以HNF-4α表达为标志）和胆管细胞（以CK19表达为标志），表明这些细胞来源于表达Foxl1-Cre的细胞。Foxl1-Cre表达细胞与肝星状细胞、门静脉成纤维细胞和肌成纤维细胞不同，尽管它们位于门静脉成纤维细胞附近。这些结果表明，早期Foxl1-Cre谱系细胞在肝损伤后产生胆管细胞和肝细胞，并提示祖-门静脉成纤维细胞相互作用的可能性。结论：Foxl1是小鼠肝脏兼性祖细胞的真正标志物。
The liver contains a population of small bipotential facultative progenitor cells that reconstitute liver function when mature hepatocytes and/or cholangiocytes are unable to proliferate. Mesenchymal markers, including members of the forkhead transcription factor gene family, have been detected in hepatic progenitor cells. The winged helix transcription factor Foxl1 localizes to mesenchymal cells in the intestine; however its expression in the liver has not been reported. We found that Foxl1 is expressed in rare cells in the normal liver but is dramatically induced in the livers of mice that have undergone bile duct ligation or were fed a DDC-containing or CDE diet. In addition, we employed genetic lineage tracing using a Foxl1-Cre transgenic mouse crossed with the Rosa26R lacZ reporter line to demonstrate that Foxl1-Cre-expressing cells are present within the periportal region shortly following injury. These cells give rise to both hepatocytes (marked by HNF-4α expression) and cholangiocytes (marked by CK19 expression), indicating that these cells were derived from Foxl1-Cre expressing cells. Foxl1-Cre expressing cells are distinct from hepatic stellate cells, portal fibroblasts and myofibroblasts, although they are located in close proximity to portal fibroblasts. These results demonstrate that the early Foxl1-Cre lineage cell gives rise to both cholangiocytes and hepatocytes following liver injury and suggest the potential for progenitor-portal fibroblast cell interactions. Conclusion: We propose that Foxl1 is a bona fide marker of the facultative progenitor cell in the mouse liver.
登录
查看更多内容
影响因子：
4.8
作者：
Perreault, N;Katz, JP;Kaestner, KH
通讯作者：
Kaestner, KH
影响因子：
5
作者：
Lorena, D;Darby, IA;Desmoulière, A
通讯作者：
Desmoulière, A
影响因子：
4
作者：
Inada, Mari;Follenzi, Antonia;Gupta, Sanjeev
通讯作者：
Gupta, Sanjeev
影响因子：
10.5
作者：
Perreault, N;Sackett, SD;Kaestner, KH
通讯作者：
Kaestner, KH
影响因子：
13.5
作者：
Kuwahara, Reiichiro;Kofman, Alexander V.;Theise, Neil D.
通讯作者：
Theise, Neil D.