新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 干细胞&iPS » Cell Research:GATA家族成员蛋白诱导iPS重编程新机制

Cell Research:GATA家族成员蛋白诱导iPS重编程新机制

来源:生物谷 2015-01-24 13:15

2015年1月24日讯 /生物谷BIOON/ --GATA蛋白家族成员在谱系分化和转分化过程中发挥着重要作用,例如在1型、2型效应T细胞的分化过程中。之前研究通过大规模筛选发现,细胞重编程中至关重要的干性因子OCT4能够被调控中内胚层(ME)发育和分化的因子(如GATA3,GATA6,PAX1)代替。但是细胞谱系分化特异性线索与多能性激活之间的联系以及GATA蛋白如何调整两者之间平衡,而且在诱导过程中,如何促进体细胞向诱导多能干细胞(iPS,induced pluripotent stem cells)的重编程,其作用机制尚不明确。一项由中国科学院北京基因组研究所孙英丽研究组与北京大学邓宏魁研究组共同完成的研究揭示了详细的分子机制。

研究人员发现所有的GATA家族成员(GATA1-GATA6)均可替代Oct4诱导细胞多能性,且对重编程过程中不同诱导阶段细胞的基因时空表达谱进行分析,发现GATA蛋白可以抑制外胚层谱系基因表达的升高从而使细胞命运走向多能性。通过结构域的研究发现GATA家族蛋白C末端锌指结构一个保守的DNA结合结构域对GATA家族成员诱导细胞多能性至关重要。利用RNA-Seq和ChIP-Seq综合分析,研究人员发现多能性相关因子Sall4是GATA家族成员诱导重编程的直接靶标并作为一个桥梁将谱系分化因子GATA成员链接至多能性作用通路。

这项研究阐明了GATA蛋白诱导iPS重编程的重要作用及内在机制,也提示GATA蛋白在细胞命运转化过程中作为媒介发挥着重要作用。(生物谷Bioon.com)

本文系生物谷原创编译整理,欢迎转载!转载请注明来源并附原文链接。谢谢!

生物谷推荐的英文摘要:

 

doi: 10.1038/cr.2015.6

GATA family members as inducers for cellular reprogramming to pluripotency


Jian Shu1,*, Ke Zhang1,2,*, Minjie Zhang3,4,*, Anzhi Yao1, Sida Shao1, Fengxia Du3, Caiyun Yang3, Wenhan Chen1, Chen Wu1, Weifeng Yang5, Yingli Sun3 and Hongkui Deng1,6,7

Members of the GATA protein family play important roles in lineage specification and transdifferentiation. Previous reports show that some members of the GATA protein family can also induce pluripotency in somatic cells by substituting for Oct4, a key pluripotency-associated factor. However, the mechanism linking lineage-specifying cues and the activation of pluripotency remains elusive. Here, we report that all GATA family members can substitute for Oct4 to induce pluripotency. We found that all members of the GATA family could inhibit the overrepresented ectodermal-lineage genes, which is consistent with previous reports indicating that a balance of different lineage-specifying forces is important for the restoration of pluripotency. A conserved zinc-finger DNA-binding domain in the C-terminus is critical for the GATA family to induce pluripotency. Using RNA-seq and ChIP-seq, we determined that the pluripotency-related gene Sall4 is a direct target of GATA family members during reprogramming and serves as a bridge linking the lineage-specifying GATA family to the pluripotency circuit. Thus, the GATA family is the first protein family of which all members can function as inducers of the reprogramming process and can substitute for Oct4. Our results suggest that the role of GATA family in reprogramming has been underestimated and that the GATA family may serve as an important mediator of cell fate conversion.

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库