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