Wandzioch Ewa, Zaret Kenneth S
Cell and Developmental Biology Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Science. 2009 Jun 26;324(5935):1707-10. doi: 10.1126/science.1174497.
Studies of the formation of pancreas and liver progenitors have focused on individual inductive signals and cellular responses. Here, we investigated how bone morphogenetic protein, transforming growth factor-beta (TGFbeta), and fibroblast growth factor signaling pathways converge on the earliest genes that elicit pancreas and liver induction in mouse embryos. The inductive network was found to be dynamic; it changed within hours. Different signals functioned in parallel to induce different early genes, and two permutations of signals induced liver progenitor domains, which revealed flexibility in cell programming. Also, the specification of pancreas and liver progenitors was restricted by the TGFbeta pathway. These findings may enhance progenitor cell specification from stem cells for biomedical purposes and can help explain incomplete programming in stem cell differentiation protocols.
对胰腺和肝脏祖细胞形成的研究主要集中在单个诱导信号和细胞反应上。在此，我们研究了骨形态发生蛋白、转化生长因子-β（TGFβ）和成纤维细胞生长因子信号通路如何汇聚到引发小鼠胚胎胰腺和肝脏诱导的最早基因上。发现诱导网络是动态的；它在数小时内就会发生变化。不同的信号并行发挥作用以诱导不同的早期基因，并且两种信号排列诱导了肝脏祖细胞区域，这揭示了细胞编程的灵活性。此外，胰腺和肝脏祖细胞的特化受到TGFβ信号通路的限制。这些发现可能会增强从干细胞中获得用于生物医学目的的祖细胞特化能力，并有助于解释干细胞分化方案中不完全编程的现象。
