英國科學(xué)家最新研究發(fā)現(xiàn),，維持胚胎干細(xì)胞多功能性的關(guān)鍵蛋白Oct4在其水平下降時會誘發(fā)胚胎干細(xì)胞進行自我更新,，從而使干細(xì)胞數(shù)量保持在一個均衡狀態(tài),。相關(guān)研究成果發(fā)表在《細(xì)胞—干細(xì)胞》雜志上。
作為維持胚胎干細(xì)胞多能性的關(guān)鍵蛋白,，Oct4控制著胚胎形成早期的基因表達,，在保證多功能干細(xì)胞數(shù)量方面扮演著至關(guān)重要的角色。過去科學(xué)家一直認(rèn)為,，一旦這種蛋白水平降低,，就會使得新生干細(xì)胞的數(shù)量隨之下降。
在最新研究中,，英國愛丁堡大學(xué)研究人員發(fā)現(xiàn),，當(dāng)Oct4水平下降之后，其會與干細(xì)胞中的基因綁定得更加緊密,，使可導(dǎo)致多功能干細(xì)胞再生的關(guān)鍵基因得到更有效的表達,，進而促使干細(xì)胞自我更新。
這一最新發(fā)現(xiàn)不僅增進了科學(xué)家對細(xì)胞分裂,、增殖過程的理解,，也有助于改進實驗室干細(xì)胞的培養(yǎng)方式，對干細(xì)胞研究具有重要意義,。（生物谷Bioon.com）
10.1016/j.stem.2013.04.023
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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.
