Differentiation phenotypes of pancreatic islet β- and α-cells are closely related with homeotic genes and a group of differentially expressed genes

Differentiation phenotypes of pancreatic islet β- and α-cells are closely related with homeotic genes and a group of differentially expressed genes
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DOI:
10.1016/j.gene.2004.01.016
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发表时间:
2004-04-28
期刊:
影响因子:
3.5
通讯作者:
Yoshimoto, K
Yoshimoto, K
中科院分区:
生物学3区
文献类型:
--
作者:
Mizusawa, N;Hasegawa, T;Yoshimoto, K

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为了确定决定分化表型的基因,我们比较了胰岛β细胞和α细胞的基因表达,这些细胞源自共同的前体细胞,分别分泌胰岛素和胰高血糖素。在 MIN6 和 alphaTC1.6 的 β 和 α 细胞系中,比较了同源基因的表达水平,包括已知确定前后 (AP) 身体轴区域特异性的 Hox 基因、组织特异性同源盒基因和其他 8,734 个基因。使用与同源域内不变氨基酸序列相对应的简并引物,然后使用特异性引物,通过逆转录聚合酶链式反应(RT-PCR)调查同源基因的表达。 MIN6 中 Hoxc6、Hoxc9、Hoxc10、Pdx1、Cdx2、Gbx2、Pax4 和 Hlxb9 基因的表达量高于 alphaTC1.6,而 Hoxa2、Hoxa3、Hoxa5、Hoxa6、Hoxa7、Hoxa9、Hoxa10、Hoxa13、Hoxb3、Hoxb5、Hoxb6、 alphaTC1.6 中的 Hoxb13、Hoxb8 和 Brain4 基因高于 MIN6。在使用高密度小鼠 cDNA 微阵列筛选 MIN6 和 alphaTC1.6 衍生 cDNA 的 8,734 个小鼠基因中,分别有 58 个和 25 个基因在 MIN6 中差异表达过表达和表达不足。 GLUTag 源自大肠肿瘤,表达胰高血糖素原基因,在 cDNA 微阵列分析的同源基因和其他基因中显示出与 alphaTC1.6 相对相似的表达谱。我们的结果与以下解释一致:不仅组织特异性同源基因,而且 Hox 基因与胰腺 β 和 α 细胞的分化表型相关,而不是与脊椎动物身体的区域规范相关。 (C) 2004 Elsevier B.V. 保留所有权利。
To identify the genes that determine differentiation phenotypes, we compared gene expression of pancreatic islet beta- and alpha-cells, which are derived from the common precursor and secrete insulin and glucagon, respectively. The expression levels of homeotic genes including Hox genes known to determine region specificity in the antero-posterior (AP) body axis, tissue-specific homeobox genes, and other 8,734 genes were compared in a beta- and alpha-cell line of MIN6 and alphaTC1.6. The expression of homeotic genes were surveyed with reverse transcription-polymerase chain reaction (RT-PCR) using degenerate primers corresponding to invariant amino acid sequences within the homeodomain and subsequently with specific primers. Expression of Hoxc6, Hoxc9, Hoxc10, Pdx1, Cdx2, Gbx2, Pax4, and Hlxb9 genes in MIN6 was higher than those in alphaTC1.6, while expression of Hoxa2, Hoxa3, Hoxa5, Hoxa6, Hoxa7, Hoxa9, Hoxa10, Hoxa13, Hoxb3, Hoxb5, Hoxb6, Hoxb13, Hoxb8, and Brain4 genes in alphaTC1.6 was higher than those in MIN6. Out of 8,734 mouse genes screened with high-density mouse cDNA microarrays for MIN6- and alphaTC1.6-derived cDNA, 58 and 25 genes were differentially over- and under-expressed in MIN6, respectively. GLUTag, which is derived from a large bowel tumor and expresses the proglucagon gene, showed a comparatively similar expression profile to that of alphaTC1.6 in both homeotic and other genes analyzed in cDNA microarray.Our results are consistent with the interpretation that not only the tissue-specific homeotic genes, but also Hox genes are related to differentiation phenotypes of pancreatic beta- and alpha-cells rather than their regional specification of the body in vertebrates. (C) 2004 Elsevier B.V. All rights reserved.