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Cell Stem Cell:Oct4蛋白可助胚胎干细胞自我更新

来源:《细胞—干细胞》 2013-05-11 10:31

英国科学家最新研究发现,维持胚胎干细胞多功能性的关键蛋白Oct4在其水平下降时会诱发胚胎干细胞进行自我更新,从而使干细胞数量保持在一个均衡状态。相关研究成果发表在《细胞—干细胞》杂志上。

作为维持胚胎干细胞多能性的关键蛋白,Oct4控制着胚胎形成早期的基因表达,在保证多功能干细胞数量方面扮演着至关重要的角色。过去科学家一直认为,一旦这种蛋白水平降低,就会使得新生干细胞的数量随之下降。

在最新研究中,英国爱丁堡大学研究人员发现,当Oct4水平下降之后,其会与干细胞中的基因绑定得更加紧密,使可导致多功能干细胞再生的关键基因得到更有效的表达,进而促使干细胞自我更新。

这一最新发现不仅增进了科学家对细胞分裂、增殖过程的理解,也有助于改进实验室干细胞的培养方式,对干细胞研究具有重要意义。(生物谷Bioon.com)

Reduced Oct4 Expression Directs a Robust Pluripotent State with Distinct Signaling Activity and Increased Enhancer Occupancy by Oct4 and Nanog

Violetta Karwacki-Neisius, Jonathan G?ke, Rodrigo Osorno, Florian Halbritter, Jia Hui Ng, Andrea Y. Wei?e, Frederick C.K. Wong, Alessia Gagliardi, Nicholas P. Mullin, Nicola Festuccia, Douglas Colby, Simon R. Tomlinson, Huck-Hui Ng, Ian Chambers

Embryonic stem cell (ESC) pluripotency is governed by a gene regulatory network centered on the transcription factors Oct4 and Nanog. To date, robust self-renewing ESC states have only been obtained through the chemical inhibition of signaling pathways or enforced transgene expression. Here, we show that ESCs with reduced Oct4 expression resulting from heterozygosity also exhibit a stabilized pluripotent state. Despite having reduced Oct4 expression, Oct4+/? ESCs show increased genome-wide binding of Oct4, particularly at pluripotency-associated enhancers, homogeneous expression of pluripotency transcription factors, enhanced self-renewal efficiency, and delayed differentiation kinetics. Cells also exhibit increased Wnt expression, enhanced leukemia inhibitory factor (LIF) sensitivity, and reduced responsiveness to fibroblast growth factor. Although they are able to maintain pluripotency in the absence of bone morphogenetic protein, removal of LIF destabilizes pluripotency. Our findings suggest that cells with a reduced Oct4 concentration range are maintained in a robust pluripotent state and that the wild-type Oct4 concentration range enables effective differentiation.

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