β-catenin regulates mesenchymal progenitor cell differentiation during hepatogenesis.
β-catenin regulates mesenchymal progenitor cell differentiation during hepatogenesis.
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DOI：
10.1016/j.jss.2009.10.033
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Wang KS
中科院分区：
文献类型：
--
作者：
Berg T;DeLanghe S;Al Alam D;Utley S;Estrada J;Wang KS
了解肝发生过程中调节间充质祖细胞命运的途径，可能有助于了解出生后肝损伤或肝生物工程。虽然β-Catenin与胎儿肝上皮祖细胞的增殖有关，但其在肝发生过程中的间充质前体细胞中的作用尚未确定。我们利用小鼠真皮1位点（β-CateninDermo1）在间质中条件缺失β-Catenin模型来表征肝发生过程中β-Catenin在肝间质中的作用。使用LacZ报告细胞的谱系追踪表明，肝星状细胞和周细胞都来源于表达间充质Dermo1的前体细胞。与对照组仔鼠肝脏相比，β-CateninDermo1胚胎肝脏更小，充满扩张的窦。虽然与同窝对照相比，β-CateninDermo1胚胎中间充质来源细胞的比例没有变化，但间充质标志物DESMIN、α-SMA和I型胶原的细胞外沉积的表达有所增加，尤其是集中在扩张的窦状体周围。对β-CateninDermo1/Flk1lacZ胚胎内皮细胞区室的分析显示肝内血管系统有明显的重组。对内胚层来源的肝母细胞群体的各种标志物的分析显示，泛细胞角蛋白的空间表达模式有明显的变化，但E-CADHERIN或白蛋白的空间表达模式没有变化。β-CateninDermo1表型显示Pitx2的间充质缺失，Pitx2是器官发生和出生后损伤期间肝间充质分化的已知调节因子。我们的数据提示肝间充质β-Catenin信号通路可能通过Pitx2参与肝间充质祖细胞在器官发生过程中的分化。反过来，肝间充质β-Catenin信号通路可能通过其他下游旁分泌途径调节内皮细胞和内胚层来源的肝母细胞的发育。
Understanding the pathways regulating mesenchymal progenitor cell fate during hepatogenesis may provide insight into postnatal liver injury or liver bioengineering. While β-Catenin has been implicated in the proliferation of fetal hepatic epithelial progenitor cells, its role in mesenchymal precursors during hepatogenesis has not been established. We used a murine model of conditional deletion of β-Catenin in mesenchyme using the Dermo1 locus (β-CateninDermo1) to characterize the role of β-Catenin in liver mesenchyme during hepatogenesis. Lineage tracing using a LacZ reporter indicates that both hepatic stellate cells and pericytes derive from mesenchymal Dermo1 expressing precursor cells. Compared to control littermate livers, β-CateninDermo1 embryonic livers are smaller and filled with dilated sinusoids. While the fraction of mesenchymally-derived cells in β-CateninDermo1 embryos is unchanged compared to littermate controls, there is an increase in the expression of the mesenchymal markers, DESMIN, α-SMA, and extracellular deposition of COLLAGEN type I, particularly concentrated around dilated sinusoids. Analysis of the endothelial cell compartment in β-CateninDermo1/Flk1lacZ embryos revealed a marked reorganization of the intrahepatic vasculature. Analysis of various markers for the endodermally-derived hepatoblast population revealed marked alterations in the spatial expression pattern of pan-CYTOKERATIN but not E-CADHERIN, or ALBUMIN. β-CateninDermo1 phenocopies mesenchymal deletion of Pitx2, a known regulator of hepatic mesenchymal differentiation both during both organogenesis and postnatal injury. Our data implicate Mesenchymal β-Catenin signaling pathway in the differentiation of liver mesenchymal progenitor cells during organogenesis, possibly via Pitx2. Hepatic Mesenchymal β-Catenin signaling, in turn, modulates the development of both endothelium and endodermally-derived hepatoblasts, presumably via other downstream paracrine pathways.
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DOI：
10.1016/j.bbrc.2007.12.085
发表时间：
2008-02-29
影响因子：
3.1
作者：
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