Analyses of cell-cell interaction regulating proliferation and differentiation of hepatic stem cells during early-liver development

在小鼠胚胎第9天左右，肝芽中的肝干/祖细胞(HSPC)被认为迁移到横隔间充质内。胎中肝(E11.5-E14.5)支持来自主动脉-性腺-中肾区域的造血干细胞的增殖和分化。我们建立了一种新的共培养系统，使用小鼠胚胎成纤维细胞来分析早期胎儿HSPC候选细胞的表型。在该共培养体系中，从小鼠胎肝(E9.5和E10.5)中分离纯化的CD13+DLK^+细胞形成白蛋白阳性肝细胞和细胞角蛋白(CK)19阳性胆管细胞组成的集落，表明CD13^+DLK^+细胞具有双能祖细胞的特性。这些对早期胎儿HSPC候选细胞的前瞻性研究表明，在E11.5之前就存在双能干/祖细胞。

Hepatic stem/progenitor cells (HSPCs) in the liver bud are postulated to migrate into septum transversum mesenchyme at around embryonic day (E) 9 in mice. Mid-fetal livers (E11.5-E14.5) support proliferation and differentiation of hematopoietic stem cells derived from the aorta-gonad-mesonephros region. We established a new co-culture system, using mouse embryonic fibroblast cells, to permit analysis of the phenotypes of early-fetal HSPC candidates. In this co-culture system, CD13^+Dlk^+ cells purified from mouse early-fetal livers (E9.5 and E10.5) formed colonies composed of both albumin-positive hepatocytic cells and cytokeratin (CK) 19-positive cholangiocytic cells, indicating that early-fetal CD13^+Dlk^+ cells have properties of bi-potent progenitor cells. These first prospective studies of early-fetal HSPC candidates demonstrate that bi-potent stem/progenitor cells exist before E11.5.