Expression of Reg Family Proteins in Embryonic Stem Cells and Its Modulation by Wnt/β-Catenin Signaling
Expression of Reg Family Proteins in Embryonic Stem Cells and Its Modulation by Wnt/β-Catenin Signaling
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DOI：
10.1089/scd.2009.0398
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发表时间：
2010-09-01
影响因子：
4
通讯作者：
Tzanakakis, Emmanuel S.
中科院分区：
文献类型：
--
作者：
Jing, Donghui;Kehoe, Daniel E.;Tzanakakis, Emmanuel S.
再生胰岛（Reg）蛋白参与多种细胞类型的增殖和分化。然而，胚胎干细胞（ESC）是否表达Reg基因及其相应的蛋白质仍然未知。在这项研究中，我们探讨了小鼠胚胎干细胞（mESCs）的Reg家族成员的表达。在未分化的干细胞中检测到小鼠Reg1和Reg3 γ。此外，我们测试了胃泌素--一种在定向细胞中Reg1表达的诱导剂--是否上调了mESC中的Reg1基因。胃泌素不影响Reg1的表达，无论是在自我更新的胚胎干细胞或条件下允许其分化。此外，在各种形式的癌症中发现的Reg基因的过表达与经典Wnt/β-连环蛋白级联的失调激活有关。鉴于Wnt信号在干细胞中的重要作用，我们研究了Wnt的激活是否改变了mESC中Reg基因的表达。Wnt激活导致Reg1基因表达增加，同时分泌的Reg1蛋白量增加。最后，在暴露于可溶性Reg1或过表达Reg1基因的mESC中检查指示分化的基因的表达模式。这是第一个帐户的表达的Reg家族成员的ESC。我们的研究结果表明，典型的Wnt级联影响Reg的表达，并保证进一步研究Reg蛋白在干细胞生理学中的潜在作用。
Regenerating islet (Reg) proteins are involved in the proliferation and differentiation of diverse cell types. However, whether embryonic stem cells (ESCs) express Reg genes and their corresponding proteins remains unknown. In this study, we probed the expression of Reg family members by mouse ESCs (mESCs). Mouse Reg1 and Reg3 gamma were detected in undifferentiated stem cells. Furthermore, we tested if gastrin-an inducer of Reg1 expression in committed cells-up-regulates the Reg1 gene in mESCs. Gastrin did not affect the expression of Reg1 either in self-renewing mESCs or under conditions permitting their differentiation. Moreover, overexpression of Reg genes found in various forms of cancer has been linked to dysregulated activation of the canonical Wnt/beta-catenin cascade. Given the important roles of Wnt signaling in stem cells, we investigated if activation of Wnt alters the expression of Reg genes in mESCs. Wnt activation led to an increase in Reg1 gene expression with a concomitant increase in the amount of secreted Reg1 protein. Finally, the expression pattern of genes indicative of differentiation was examined in mESCs that were either exposed to soluble Reg1 or overexpressed the Reg1 gene. This is the first account of expression of Reg family members by ESCs. Our results show that the canonical Wnt cascade affects Reg expression and warrants further studies into the potential roles of Reg proteins in stem cell physiology.