Transcriptome coexpression map of human embryonic stem cells.
Transcriptome coexpression map of human embryonic stem cells.
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DOI：
10.1186/1471-2164-7-103
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发表时间：
2006-05-02
期刊：
影响因子：
4.4
通讯作者：
Zhan, Ming
中科院分区：
文献类型：
--
作者：
Li, Huai;Liu, Ying;Shin, Soojung;Sun, Yu;Loring, Jeanne F;Mattson, Mark P;Rao, Mahendra S;Zhan, Ming
人类胚胎干细胞（ES）在医学和科学领域有着巨大的前景。近年来，人们对胚胎干细胞的转录组进行了详细的研究。然而，目前还没有系统的分析表明人类胚胎干细胞中的基因表达是否可能在染色体结构域中受到调节，也没有发现染色体共表达结构域。为了分析胚胎干细胞自我更新和分化过程中转录调控如何与基因组结构相互作用，我们报道了人类胚胎干细胞和胚胎分化最早阶段的转录组共表达图谱。我们确定了多个ES和EB样本的基因表达谱，并确定了基因组上显示邻近基因共表达的染色体结构域。这些共表达域不是随机的，在ES状态下的8、11、16、17、19和Y染色体上以及在EB状态下的6、11、17、19和20染色体上都有显著的富集。这些结构域在EB中与giemsa阴性带显著相关，但在ES细胞中与已知的细胞遗传学结构相关性不大。通过比较ES和EB的转录组图谱揭示了不同的共表达模式。本研究的发现和方法促进了我们对基因组组织如何影响人类胚胎干细胞基因表达的理解，并有助于确定控制胚胎干细胞自我更新或分化的新机制和途径。
Human embryonic stem (ES) cells hold great promise for medicine and science. The transcriptome of human ES cells has been studied in detail in recent years. However, no systematic analysis has yet addressed whether gene expression in human ES cells may be regulated in chromosomal domains, and no chromosomal domains of coexpression have been identified. We report the first transcriptome coexpression map of the human ES cell and the earliest stage of ES differentiation, the embryoid body (EB), for the analysis of how transcriptional regulation interacts with genomic structure during ES self-renewal and differentiation. We determined the gene expression profiles from multiple ES and EB samples and identified chromosomal domains showing coexpression of adjacent genes on the genome. The coexpression domains were not random, with significant enrichment in chromosomes 8, 11, 16, 17, 19, and Y in the ES state, and 6, 11, 17, 19 and 20 in the EB state. The domains were significantly associated with Giemsa-negative bands in EB, yet showed little correlation with known cytogenetic structures in ES cells. Different patterns of coexpression were revealed by comparative transcriptome mapping between ES and EB. The findings and methods reported in this investigation advance our understanding of how genome organization affects gene expression in human ES cells and help to identify new mechanisms and pathways controlling ES self-renewal or differentiation.