Sherwood Richard I, Chen Tzong-Yang Albert, Melton Douglas A
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Dev Dyn. 2009 Jan;238(1):29-42. doi: 10.1002/dvdy.21810.
Although endodermal organs including the liver, pancreas, and intestine are of significant therapeutic interest, the mechanism by which the endoderm is divided into organ domains during embryogenesis is not well understood. To better understand this process, global gene expression profiling was performed on early endodermal organ domains. This global analysis was followed up by dynamic immunofluorescence analysis of key transcription factors, uncovering novel expression patterns as well as cell surface proteins that allow prospective isolation of specific endodermal organ domains. Additionally, a repressive interaction between Cdx2 and Sox2 was found to occur at the prospective stomach-intestine border, with the hepatic and pancreatic domains forming at this boundary, and Hlxb9 was revealed to have graded expression along the dorsal-ventral axis. These results contribute to understanding the mechanism of endodermal organogenesis and should assist efforts to replicate this process using pluripotent stem cells.
尽管包括肝脏、胰腺和肠道在内的内胚层器官具有重大的治疗意义,但在胚胎发育过程中内胚层如何分化为器官区域的机制仍未得到充分理解。为了更好地理解这一过程,对早期内胚层器官区域进行了全基因组表达谱分析。在此全局分析之后,对关键转录因子进行了动态免疫荧光分析,揭示了新的表达模式以及能够对特定内胚层器官区域进行前瞻性分离的细胞表面蛋白。此外,发现Cdx2和Sox2之间在前胃-肠边界处发生抑制性相互作用,肝脏和胰腺区域在此边界形成,并且Hlxb9沿背腹轴呈梯度表达。这些结果有助于理解内胚层器官发生的机制,并应有助于利用多能干细胞复制这一过程的努力。