Embryonic Ductal Plate Cells Give Rise to Cholangiocytes, Periportal Hepatocytes, and Adult Liver Progenitor Cells

被引:188
作者
Carpentier, Rodolphe [1 ]
Suner, Regina Espanol [2 ]
van Hul, Noemi [2 ]
Kopp, Janel L. [3 ]
Beaudry, Jean-Bernard [1 ]
Cordi, Sabine [1 ]
Antoniou, Aline [1 ]
Raynaud, Peggy [1 ]
Lepreux, Sebastien [4 ]
Jacquemin, Patrick [1 ]
Leclercq, Isabelle A.
Sander, Maike [3 ]
Lemaigre, Frederic P. [1 ]
机构
[1] Catholic Univ Louvain, de Duve Inst, B-1200 Brussels, Belgium
[2] Catholic Univ Louvain, Inst Rech Expt & Clin, B-1200 Brussels, Belgium
[3] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
[4] Univ Bordeaux Segalen, INSERM, Unite BioTis 1026, Bordeaux, France
基金
美国国家卫生研究院;
关键词
Hepatic Cell Differentiation; Liver Development; Liver Regeneration; INTRAHEPATIC BILE-DUCTS; HEPATIC STEM-CELLS; GENE-EXPRESSION; MOUSE-LIVER; REGENERATION; MICROARRAYS; PANCREAS; FETAL;
D O I
10.1053/j.gastro.2011.06.049
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND& AIMS: Embryonic biliary precursor cells form a periportal sheet called the ductal plate, which is progressively remodeled to generate intrahepatic bile ducts. A limited number of ductal plate cells participate in duct formation; those not involved in duct development are believed to involute by apoptosis. Moreover, cells that express the SRY-related HMG box transcription factor 9 (SOX9), which include the embryonic ductal plate cells, were proposed to continuously supply the liver with hepatic cells. We investigated the role of the ductal plate in hepatic morphogenesis. METHODS: Apoptosis and proliferation were investigated by immunostaining of mouse and human fetal liver tissue. The postnatal progeny of SOX9-expressing ductal plate cells was analyzed after genetic labeling, at the ductal plate stage, by Cre-mediated recombination of a ROSA26R(YFP) reporter allele. Inducible Cre expression was induced by SOX9 regulatory regions, inserted in a bacterial artificial chromosome. Livers were studied from mice under normal conditions and during diet-induced regeneration. RESULTS: Ductal plate cells did not undergo apoptosis and showed limited proliferation. They generated cholangiocytes lining interlobular bile ducts, bile ductules, and canals of Hering, as well as periportal hepatocytes. Oval cells that appeared during regeneration also derived from the ductal plate. We did not find that liver homeostasis required a continuous supply of cells from SOX9-expressing progenitors. CONCLUSIONS: The ductal plate gives rise to cholangiocytes lining the intrahepatic bile ducts, including its most proximal segments. It also generates periportal hepatocytes and adult hepatic progenitor cells.
引用
收藏
页码:1432 / U902
页数:11
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