Developmental pathways during in vitro progression of human islet neogenesis.
Developmental pathways during in vitro progression of human islet neogenesis.
复制标题
人类胰岛新发生的体外进展过程中的发育途径。
DOI：
10.1016/j.diff.2008.09.015
复制
发表时间：
2009-02
期刊：
影响因子：
2.9
通讯作者：
Bonner-Weir, Susan
中科院分区：
文献类型：
--
作者：
Dodge, Rikke;Loomans, Cindy;Sharma, Arun;Bonner-Weir, Susan
胰岛新生，或胰岛细胞从前体细胞的分化，在体外和体内胚胎和出生后都可以看到。然而，对人胰腺胚胎发育过程中的分化途径知之甚少。我们先前报道的从人胰腺组织中体外生成胰岛提供了一个独特的系统来鉴定新生的潜在标志物并确定该过程的分子机制。为此，我们分析了体外胰岛生成过程中三个不同阶段的基因表达谱：初始粘附阶段、扩增阶段和分化阶段。将来自四个人胰腺的样品与Affyssin U95 A基因芯片杂交，并使用GeneSpring 7.0/9.0软件分析数据。使用散点图，我们选择具有2倍或更大差异表达的基因。在这些阵列上存在的12，000个基因/EST中，包括38个腺泡富集基因的295个基因在从初始粘附阶段到扩展阶段的进展期间选择性地丢失; 468个基因在扩展组织的进展中增加;并且529个基因在分化阶段中的表达比在扩展组织中的表达高两倍。除了胰岛素、胰高血糖素和导管标志物（粘蛋白6、水通道蛋白1和5）的预期增加之外，β细胞自身抗原IA-2/phogrin在分化中增加5倍。此外，在扩增/分化过程中，包括Notch/jagged、Wnt/Frizzled、TGFβ超家族（卵泡抑素、BMP和SMAD）、视黄酸（COUP-TFI、CRABP 1、2和RAIG 1）在内的发育重要途径受到差异调节。两个公认的胰岛前体细胞的标志物，UCHL 1/PGP9.5和DMBT 1，在向分化细胞的进展过程中增强，但只有后者可以是胰岛前体细胞的标志物。我们认为，这些分化相关的途径的适当操作将提高在这个体外模型中的胰岛素产生β细胞的分化效率。
Islet neogenesis, or the differentiation of islet cells from precursor cells, is seen in vitro and in vivo both embryonically and after birth. However, little is known about the differentiation pathways during embryonic development for human pancreas. Our previously reported in vitro generation of islets from human pancreatic tissue provides a unique system to identify potential markers of neogenesis and to determine the molecular mechanisms underlying this process. To this end, we analyzed the gene expression profiles of three different stages during in vitro islet generation: the Initial Adherent-, Expanded-, and Differentiated- stages. Samples from four human pancreases were hybridized to Affymetrix U95A GeneChips, and data analyzed using GeneSpring 7.0/9.0 software. Using Scatter plots we selected genes with a 2-fold or greater differential expression.. Of the 12,000 genes/ESTs present on these arrays, 295 genes including 38 acinar–enriched genes were selectively lost during the progression from the Initially Adherent stage to the Expanded stage; 468 genes were increased in this progression to Expanded tissue; and 529 genes had a two-fold greater expression in the Differentiated-stage than in the Expanded tissue. Besides the expected increases in insulin, glucagon and duct markers (mucin 6, aquaporin 1 and 5), the beta cell auto-antigen IA-2/phogrin was increased 5-fold in Differentiated. In addition developmentally important pathways, including Notch/jagged, Wnt/Frizzled, TGFβ superfamily (follistatin, BMPs and SMADs), retinoic acid (COUP-TFI, CRABP1, 2 and RAIG1) were differentially regulated during the expansion/differentiation. Two putative markers for islet precursor cells, UCHL1/PGP9.5 and DMBT1, were enhanced during the progression to differentiated cells, but only the latter could be a marker of islet precursor cells. We suggest that appropriate manipulation of these differentiation-associated pathways will enhance the efficiency of differentiation of insulin-producing beta cells in this in vitro model.
登录
查看更多内容
影响因子：
4.6
作者：
Esni, F;Ghosh, B;Leach, SD
通讯作者：
Leach, SD
影响因子：
64.8
作者：
Apelqvist, Å;Li, H;Edlund, H
通讯作者：
Edlund, H
DOI：
10.1073/pnas.96.19.10794
发表时间：
1999-09-14
影响因子：
11.1
作者：
Holmskov, U;Mollenhauer, J;Skjodt, K
通讯作者：
Skjodt, K
慢性高血糖引发糖尿病动物模型胰腺β细胞分化丧失
影响因子：
4.8
作者：
Jonas, JC;Sharma, A;Weir, GC
通讯作者：
Weir, GC
影响因子：
7.3
作者：
Leung, WK;Yu, J;Sung, JJY
通讯作者：
Sung, JJY