PTHRP/Adenylate cyclase promotes parietal whereas Wnt/ß-catenin signaling promotes visceral endoderm differentiation of rat XEN cells.

In this study we showed that rat XEN cells grown in the presence of a GSK3 inhibitor exhibited enhanced formation of cell contacts and decreased motility. In contrast, treatment with forskolin induced the PE formation and epithelial-mesenchymal transition (EMT) in rat XEN cells. Using microarray and real-time PCR assays, we found that VE versus PE formation of rat XEN cells was correlated with change in expression levels of VE or PE marker genes. Similar to forskolin, EMT was prompted upon treatment of rat XEN cells with recombinant parathyroid hormone related peptide (PTHRP), an activator of the cAMP pathway in vivo. Taken together, our data suggest that rat XEN cells are PrE-like cells. The activation of Wnt pathway in rat XEN cells leads to the acquisition of VE characteristics, whereas the activation of the PTHRP/cAMP pathway leads to EMT and the formation of PE.本研究证实，在糖原合成激酶3抑制剂（GSK3 inhibitor）存在的培养体系中生长的大鼠XEN细胞（rat XEN cells），其细胞连接形成能力增强且运动能力降低。与之相反，经佛司可林（forskolin）处理的大鼠XEN细胞可诱导原始内胚层（primitive endoderm, PE）形成与上皮间质转化（epithelial-mesenchymal transition, EMT）。通过基因芯片（microarray）与实时荧光定量PCR（real-time PCR）实验，我们发现大鼠XEN细胞的内脏内胚层（visceral endoderm, VE）与原始内胚层（PE）形成过程，与VE或PE标记基因的表达水平变化显著相关。与佛司可林类似，经重组甲状旁腺激素相关肽（recombinant parathyroid hormone related peptide, PTHRP，一种体内环磷酸腺苷通路（cAMP pathway）的激活剂）处理大鼠XEN细胞后，亦可诱导EMT发生。综上，本研究数据表明大鼠XEN细胞属于原始内胚层样（PrE-like）细胞。大鼠XEN细胞中Wnt通路（Wnt pathway）的激活可使其获得VE相关特性，而PTHRP/cAMP通路的激活则会引发EMT并诱导PE形成。