小鼠胚胎干细胞在胎肾微环境中共培养后表达肾标志物

胚胎干（ES）细胞是一种多潜能细胞具有分化成为来自三个胚层各种细胞甚至包括生殖细胞的能力。最新的研究表明，胚胎于细胞在与胚胎脏器细胞共培养后可以定向分化为多种特定细胞表型，他们包括肝细胞、心肌细胞和Ⅱ型肺泡上皮细胞．并在某些情况下甚至可能形成成熟的器官组织结构。已有研究报道说明ES细胞通过在体外环境中直接形成拟胚体（EBs）可以分化成为肾细胞．并且最新的研究成果表明分离自这些EBs的细胞移植入体内后可以形成肾近端小管样结构并且未在其周同发现畸胎瘤形成。但是ES细胞是否可以通过和胎肾细胞相互作用继而获得定向分化并未见诸报道。在实验中我们发现．在与小鼠胎肾细胞共培养后．ES细胞分化成为了肾系细胞。处理后的ES细胞可以检测到与肾发育相关的特征基因．如WT-1、exm-2和Wnt-4基因的表达．我们也发现了终末分化的肾细胞标志物．如podocalyxin、Nephl和RSOR基因的表达。在实验前后，我们同样探寻了ES细胞多分化潜能标记分子的基因表达情况，结果显示共培养后分化的ES细胞Oct-4、Nanog和Klf-4基因表达明显减弱。综上，胎肾细胞微环境可能促使ES细胞定向分化为肾系细胞，提示胚胎器官细胞微环境在ES细胞转分化过程中可能扮演了重要作用。

Mouse embryonic stem cells express kidney marker molecules following co-culture in fetal renal microenvironment

Embryonic stem (Es) cells are known to be pluripotent becallse of their capability to differentiate into cell types of all three germ layers including germ cells.Recent studies have demonstrated that ES cells are potential to differentiate into a broad spectrum of specialized cell types,including hepatocyte,cardiomyocyte and alveolar epithelial type Ⅱ cell types and some even form the mature structures after co-cultured with embryonic cells.Researchers have reported that ES cells could differentiate into renal lineage via embryoid bodies (EBs) in vitro,and the latest report has shown that cells isolated from that EBs formed the proximal tubules in vivo and without teratoma formation. But whether the ES cells could interact with the fetal renal cells and proceed a special differentiation hasn't been reported yet.Here, we show that ES cells probably differentiate into renal cell types via co-cultured with mouse fetal renal cells in vitro,and the treated ES cells were detected expressing marker molecules characteristic for initiation of nephrogenesis(WT-1,emx-2and Wnt-4)and terminally differentiated renal cell types (podocalyxin,Nephl and RSOR).We also investigated the gene expressions of Oct-4,Nanog and Klf-4 which are associated with the ES cells' capacity to differentiate into all kinds of cells,and found that their expression obviouslv depressed in the differentiated cells.In summary,the fetal renal cell microenvironment may lead the ES cells differentiate toward a renal lineage, it hints that the microenvironment of embryonic organic cells may play a crucial role during the transdifferentiation of ES cells.