Sox9 coordinates a transcriptional network in pancreatic progenitor cells
Sox9 coordinates a transcriptional network in pancreatic progenitor cells
复制标题
DOI：
10.1073/pnas.0704054104
复制
发表时间：
2007-06-19
影响因子：
11.1
通讯作者：
German, M. S.
中科院分区：
文献类型：
--
作者：
Lynn, F. C.;Smith, S. B.;German, M. S.
在胰腺发育过程中，外分泌和内分泌谱系都从与成熟胰管细胞相似的共同祖细胞库分化。在这些胰腺祖细胞中已经鉴定出一小组转录因子，包括Tcf 2、Onecut 1和Foxa 2。Sry/HMG盒转录因子Sox 9也在早期胰腺上皮中表达，并且是人类正常胰腺外分泌和内分泌发育所需的。在这项研究中，我们发现小鼠体内的Sox 9与成人胰腺祖细胞和导管细胞中的其他祖细胞转录因子一起特异性表达。Sox 9在体外和完整细胞中直接与所有三种基因结合，并调节其表达。反过来，Foxa 2和Tcf 2都调节Sox 9的表达，证明了这些基因之间的反馈回路。此外，Sox 9激活了前内分泌因子Neurogenin 3的表达，这也取决于祖细胞转录网络的其他成员。这些研究表明，Sox 9在胰腺祖细胞中起着双重作用：既维持稳定的转录网络，又支持这些细胞分化成不同谱系的程序。
During pancreas development, both the exocrine and endocrine lineages differentiate from a common pool of progenitor cells with similarities to mature pancreatic duct cells. A small set of transcription factors, including Tcf2, Onecut1, and Foxa2, has been identified in these pancreatic progenitor cells. The Sry/HMG box transcription factor Sox9 is also expressed in the early pancreatic epithelium and is required for normal pancreatic exocrine and endocrine development in humans. In this study, we found Sox9 in mice specifically expressed with the other progenitor transcription factors in both pancreatic progenitor cells and duct cells in the adult pancreas. Sox9 directly bound to all three genes in vitro and in intact cells, and regulated their expression. In turn, both Foxa2 and Tcf2 regulated Sox9 expression, demonstrating feedback circuits between these genes. Furthermore, Sox9 activated the expression of the proendocrine factor Neurogenin3, which also depends on the other members of the progenitor transcription network. These studies indicate that Sox9 plays a dual role in pancreatic progenitor cells: both maintaining a stable transcriptional network and supporting the programs by which these cells differentiate into distinct lineages.