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全球基因表达揭示了一组新基因,这些基因参与了红细胞分化过程中细胞的修饰。

Global gene expression reveals a set of new genes involved in the modification of cells during erythroid differentiation.

机构信息

Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.

出版信息

Cell Prolif. 2010 Jun;43(3):297-309. doi: 10.1111/j.1365-2184.2010.00679.x.

Abstract

OBJECTIVES

Erythroid differentiation is a dynamic process in which a pluripotent stem cell undergoes a series of developmental changes that commit it to a specific lineage. These alterations involve changes in gene expression profiles. In this study, gene expression profiles during differentiation of human erythroid cells of a normal blood donor were evaluated using SAGE.

MATERIALS AND METHODS

Global gene expression was evaluated in cells collected immediately before addition of erythropoietin (0 h) and 192 and 336 h after addition of this hormone. Real-time PCR was used to evaluate activation of differentially expressed genes.

RESULTS

The data indicate that global aspects of the transcriptome were similar during differentiation of the majority of the genes and that a relatively small set of genes is probably involved in modification of erythroid cells during differentiation. We have identified 93 differentially expressed genes during erythroid development, and expression of some of these was confirmed by qPCR. Various genes including EYA3, ERH, HES6, TIMELESS and TRIB3 were found to be homologous to those of Drosophila melanogaster and here are described for the first time during erythroid development. An important and unique carboxypeptidase inhibitor described in mammalians, LXN, was also identified.

CONCLUSIONS

The results of this study amplify previously published data and may contribute to comprehension of erythroid differentiation and identification of new target genes involved in some erythroid concerning diseases.

摘要

目的

红细胞分化是一个多能干细胞经历一系列发育变化的动态过程,使其向特定谱系定向。这些改变涉及基因表达谱的变化。在这项研究中,我们使用 SAGE 评估了来自正常献血者的人类红系细胞分化过程中的基因表达谱。

材料与方法

在添加红细胞生成素(0 小时)之前和添加后 192 和 336 小时收集细胞,评估细胞的全局基因表达。使用实时 PCR 评估差异表达基因的激活。

结果

数据表明,在大多数基因的分化过程中,转录组的整体方面相似,只有一小部分基因可能参与了红细胞分化过程中的修饰。我们在红细胞发育过程中鉴定了 93 个差异表达基因,其中一些基因的表达通过 qPCR 得到了验证。包括 EYA3、ERH、HES6、TIMELSS 和 TRIB3 在内的各种基因与果蝇同源,这是它们在红细胞发育过程中的首次描述。还鉴定了一种在哺乳动物中描述的重要且独特的羧肽酶抑制剂 LXN。

结论

本研究的结果扩展了先前发表的数据,并可能有助于理解红细胞分化和鉴定涉及某些红细胞相关疾病的新靶基因。

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本文引用的文献

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Pleiotropic effects in Eya3 knockout mice.Eya3基因敲除小鼠中的多效性效应。
BMC Dev Biol. 2008 Dec 22;8:118. doi: 10.1186/1471-213X-8-118.
2
The TRIB3 Q84R polymorphism and risk of early-onset type 2 diabetes.TRIB3基因Q84R多态性与早发型2型糖尿病风险
J Clin Endocrinol Metab. 2009 Jan;94(1):190-6. doi: 10.1210/jc.2008-1365. Epub 2008 Nov 4.
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Serial analysis of gene expression adapted for downsized extracts (SAGE/SADE) analysis in reticulocytes.
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Aging stem cells, latexin, and longevity.衰老干细胞、乳脂球蛋白与长寿。
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E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3.E3泛素连接酶SIAH1介导TRB3的泛素化和降解。
Cell Signal. 2008 May;20(5):942-8. doi: 10.1016/j.cellsig.2008.01.010. Epub 2008 Jan 24.

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