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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors
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Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors

机译：人类结肠顶部和基底隐窝以及BMP拮抗剂作为肠道干细胞生态位因子的基因表达模式

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Human colonic epithelial cell renewal, proliferation, and differentiation are stringently controlled by numerous regulatory pathways. To identify genetic programs of human colonic epithelial cell differentiation in vivo as well as candidate marker genes that define colonic epithelial stem/progenitor cells and the stem cell niche, we applied gene expression analysis of normal human colon tops and basal crypts by using expression microarrays with 30,000 genes. Nine hundred and sixty-nine cDNA clones were found to be differentially expressed between human colon crypts and tops. Pathway analysis revealed the differential expression of genes involved in cell cycle maintenance and apoptosis, as well as genes in bone morphogenetic protein (BMP), Notch, Wnt, EPH, and MYC signaling pathways. BMP antagonists gremlin 1, gremlin 2, and chordin-like 1 were found to be expressed by colon crypts. In situ hybridization and RT-PCR confirmed that these BMP antagonists are expressed by intestinal cryptal myofibroblasts and smooth muscle cells at the colon crypt. In vitro analysis demonstrated that gremlin 1 partially inhibits Caco-2 cell differentiation upon confluence and activates Wnt signaling in normal rat intestinal epithelial cells. Collectively, the expression data set provides a comprehensive picture of human colonic epithelial cell differentiation. Our study also suggests that BMP antagonists are candidate signaling components that make up the intestinal epithelial stem cell niche.
机译：人结肠上皮细胞的更新，增殖和分化受到众多调节途径的严格控制。为了确定体内人结肠上皮细胞分化的遗传程序以及定义结肠上皮干/祖细胞和干细胞生态位的候选标记基因，我们通过使用表达芯片将正常人结肠顶部和基底隐窝进行基因表达分析30,000个基因。发现在人结肠隐窝和顶部之间差异表达了969个cDNA克隆。途径分析揭示了参与细胞周期维持和凋亡的基因的差异表达，以及骨形态发生蛋白（BMP），Notch，Wnt，EPH和MYC信号通路中的基因。发现BMP拮抗剂gremlin 1，gremlin 2和chordin-like 1由结肠隐窝表达。原位杂交和RT-PCR证实这些BMP拮抗剂由肠隐窝成肌纤维细胞和结肠隐窝的平滑肌细胞表达。体外分析表明，gremlin 1在汇合后可部分抑制Caco-2细胞分化，并激活正常大鼠肠上皮细胞中的Wnt信号传导。总之，表达数据集提供了人类结肠上皮细胞分化的全面情况。我们的研究还表明，BMP拮抗剂是组成肠道上皮干细胞生态位的候选信号成分。

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