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首页> 外文期刊>Molecular and Cellular Biology >An intestine-specific homeobox gene regulates proliferation and differentiation.
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An intestine-specific homeobox gene regulates proliferation and differentiation.

机译：肠特异性同源盒基因调节增殖和分化。

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Precise regulation of cellular proliferation, differentiation, and senescence results in the continuous renewal of the intestinal epithelium with maintenance of a highly ordered tissue architecture. Here we show that an intestine-specific homeobox gene, Cdx2, is a transcription factor that regulates both proliferation and differentiation in intestinal epithelial cells. Conditional expression of Cdx2 in IEC-6 cells, an undifferentiated intestinal cell line, led to arrest of proliferation for several days followed by a period of growth resulting in multicellular structures containing a well-formed columnar layer of cells. The columnar cells had multiple morphological characteristics of intestinal epithelial cells. Enterocyte-like cells were polarized with tight junctions, lateral membrane interdigitations, and well-organized microvilli with associated glycocalyx located at the apical pole. Remarkably, there were also cells with a goblet cell-like ultrastructure, suggesting that two of the four intestinal epithelial cell lineages may arise from IEC-6 cells. Molecular evidence for differentiation was shown by demonstrating that cells expressing high levels of Cdx2 expressed sucrase-isomaltase, an enterocyte-specific gene which is a well-defined target for the Cdx2 protein. Taken together, our data suggest that Cdx2 may play a role in directing early processes in intestinal cell morphogenesis and in the maintenance of the differentiated phenotype by supporting transcription of differentiated gene products. We propose that Cdx2 is part of a regulatory network that orchestrates a developmental program of proliferation, morphogenesis, and gene expression in the intestinal epithelium.
机译：细胞增殖，分化和衰老的精确调节导致肠道上皮细胞不断更新，同时维持高度有序的组织结构。在这里，我们显示了肠道特异性同源盒基因Cdx2，是一种转录因子，可调节肠道上皮细胞的增殖和分化。 Cdx2在IEC-6细胞（一种未分化的肠道细胞系）中的条件表达导致几天的增殖停滞，随后一段时期的生长导致多细胞结构包含良好形成的柱状细胞层。柱状细胞具有肠上皮细胞的多种形态特征。肠上皮样细胞极化紧密连接，侧膜叉指和组织良好的微绒毛与相关的糖萼位于顶端。值得注意的是，还有一些细胞呈杯状细胞状的超微结构，这表明四个肠上皮细胞谱系中的两个可能源于IEC-6细胞。通过证明表达高水平Cdx2的细胞表达了蔗糖酶-异麦芽糖酶，这是一种肠细胞特异性基因，是Cdx2蛋白的明确靶标，从而显示出分化的分子证据。两者合计，我们的数据表明Cdx2可能在指导肠道细胞形态发生的早期过程和通过支持分化基因产物的转录维持分化表型中发挥作用。我们建议Cdx2是协调网络的一部分，在小肠上皮细胞中协调增殖，形态发生和基因表达的发育程序。

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