Section on Molecular Morphogenesis, Program in Cellular Regulation and Metabolism (PCRM), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 18 Library Dr., 20892 Bethesda, Maryland, USA.
Present address: Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, 350-1241 Hidaka-shi, Saitama, Japan.
Cell Biosci. 2013 Nov 13;3(1):43. doi: 10.1186/2045-3701-3-43.
Organ-specific, adult stem cells are essential for organ-homeostasis and tissue repair and regeneration. The formation of such stem cells during vertebrate development remains to be investigated. Frog metamorphosis offers an excellent opportunity to study the formation of adult stem cells as this process involves essentially the transformations of all larval tissues/organs into the adult form. Of particular interest is the remodeling of the intestine. Early studies in Xenopus laevis have shown that this process involves complete degeneration of the larval epithelium and de novo formation of adult stem cells through dedifferentiation of some larval epithelial cells. A major advantage of this metamorphosis model is its total dependence on thyroid hormone (T3). In an effort to identify genes that are important for stem cell development, we have previously carried out tissue-specific microarray analysis of intestinal gene expression during Xenopus laevis metamorphosis.
We report the detailed characterization of one of the genes thus identified, the histidine ammonia-lyase (HAL) gene, which encodes an enzyme known as histidase or histidinase. We show that there are two duplicated HAL genes, HAL1 and HAL2, in both Xenopus laevis and Xenopus tropicalis, a highly related but diploid species. Interestingly, only HAL2 is highly upregulated by T3 and appears to be specifically expressed in the adult intestinal progenitor/stem cells while HAL1 is not expressed in the intestine during metamorphosis. Furthermore, when analyzed in whole animals, HAL1 appears to be expressed only during embryogenesis but not metamorphosis while the opposite appears to be true for HAL2.
Our results suggest that the duplicated HAL genes have distinct functions with HAL2 likely involved in the formation and/or proliferation of the adult stem cells during metamorphosis.
器官特异性、成体干细胞对于器官稳态和组织修复与再生至关重要。脊椎动物发育过程中此类干细胞的形成仍有待研究。青蛙变态为研究成体干细胞的形成提供了极好的机会，因为这一过程本质上涉及所有幼虫组织/器官向成体形式的转变。特别引人关注的是肠道的重塑。早期对非洲爪蟾的研究表明，这一过程涉及幼虫上皮的完全退化和通过一些幼虫上皮细胞的去分化形成新的成体干细胞。该变态模型的一个主要优势是其完全依赖甲状腺激素（T3）。为了鉴定对干细胞发育重要的基因，我们先前对非洲爪蟾变态过程中肠道基因表达进行了组织特异性微阵列分析。
我们报告了在此过程中鉴定出的一个基因的详细特征，该基因为组氨酸氨裂解酶（HAL）基因，编码一种已知的酶，即组氨酸酶或组氨酸酶。我们表明，在非洲爪蟾和高度相关的二倍体物种非洲爪蟾热带种中，存在两个复制的 HAL 基因，HAL1 和 HAL2。有趣的是，只有 HAL2 被 T3 高度上调，似乎专门在成年肠道祖细胞/干细胞中表达，而 HAL1 在变态过程中不在肠道中表达。此外，当在整体动物中进行分析时，HAL1 似乎仅在胚胎发生期间表达，而在变态期间不表达，而 HAL2 则相反。
我们的结果表明，复制的 HAL 基因具有不同的功能，HAL2 可能参与了变态过程中成体干细胞的形成和/或增殖。
Zotero 插件
