Linkage of pluripotent stem cell-associated transcripts to regulatory gene networks.
Linkage of pluripotent stem cell-associated transcripts to regulatory gene networks.
复制标题
多能干细胞相关转录物与调控基因网络的联系。
DOI：
10.1159/000118787
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Boheler,KennethR
中科院分区：
文献类型：
--
作者：
Tarasov,KirillV;Testa,Gianluca;Tarasova,YelenaS;Kania,Gabriela;Riordon,DanielR;Volkova,Maria;Anisimov,SergeyV;Wobus,AnnaM;Boheler,KennethR
了解胚胎干细胞中负责多能性和自我更新的转录回路，等同于理解早期哺乳动物的发育，也是确定其治疗潜力的先决条件。各种各样的技术已经使用基因组学来鉴定干细胞中丰富的转录本，试图定义“干性”的分子基础。在这项研究中，我们扩展了传统的基因组分析，以确定可能涉及控制胚胎干细胞限制性基因启动子的顺式元件。该策略依赖于通过基因表达谱的系列分析和随后的启动子分析生成问题特异性列表，以确定问题特异性列表中基因在空间和方向上保守的多个顺式元件的框架。随后的实验数据表明，从这些模型中预测到的2个新的转录因子，B-Myb和Maz，要么参与维持未分化的干细胞状态，要么参与分化的早期步骤。
Knowledge of the transcriptional circuitry responsible for pluripotentiality and self-renewal in embryonic stem cells is tantamount to understanding early mammalian development and a prerequisite to determining their therapeutic potential. Various techniques have employed genomics to identify transcripts that were abundant in stem cells, in an attempt to define the molecular basis of ‘stemness’. In this study, we have extended traditional genomic analyses to identify cis-elements that might be implicated in the control of embryonic stem cell-restricted gene promoters. The strategy relied on the generation of a problem-specific list from serial analysis of gene expression profiles and subsequent promoter analyses to identify frameworks of multiple cis-elements conserved in space and orientation among genes from the problem-specific list. Subsequent experimental data suggest that 2 novel transcription factors, B-Myb and Maz, predicted from these models, are implicated either in the maintenance of the undifferentiated stem cell state or in early steps of differentiation.