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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Sox9 coordinates a transcriptional network in pancreatic progenitor cells
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Sox9 coordinates a transcriptional network in pancreatic progenitor cells

机译：Sox9协调胰腺祖细胞中的转录网络

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摘要

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 ceils: both maintaining a stable transcriptional network and supporting the programs by which these cells differentiate into distinct lineages.
机译：在胰腺发育过程中，外分泌谱系和内分泌谱系均与共同的祖细胞群分化，与成熟的胰管细胞相似。在这些胰腺祖细胞中已鉴定出一小套转录因子，包括Tcf2，Onecut1和Foxa2。 Sry / HMG盒转录因子Sox9在早期胰腺上皮细胞中也表达，是人类正常胰腺外分泌和内分泌发育所必需的。在这项研究中，我们发现成年胰腺中胰腺祖细胞和导管细胞中与其他祖细胞转录因子特异性表达的小鼠中的Sox9。 Sox9在体外和完整细胞中直接结合所有三个基因，并调节它们的表达。反过来，Foxa2和Tcf2都调节了Sox9的表达，证明了这些基因之间的反馈回路。此外，Sox9激活了内分泌因子Neurogenin3的表达，后者也依赖于祖细胞转录网络的其他成员。这些研究表明，Sox9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。

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