Nanog基因的生物学功能研究进展

Progress on Novel Pluripotency-Maintaining Factor Nanog

胚胎干细胞具有无限增殖能力和多向分化潜能决定了它在医学及生物学基础研究中具有巨大的应用潜力。探索维持胚胎干细胞特性的分子机制成为胚胎干细胞的生物学研究中的热点。研究发现与维持胚胎干细胞多能性相关的基因有Oct4、Nanog、Sox2等,其中Nanog是2003年5月末发现的一个基因,它对维持胚胎干细胞多能性起关键性作用,能够独立于L1F/Stats维持ICM和ES细胞的多能性。几年来,Nanog的生物学功能及其与Oct4、Sox2等多能性维持基因之间的相互作用关系已有较为深入的研究。作者在综述Nanog基因的表达特征和功能的基础上,重点探讨Nanog基因表达调控以及Oct4、Sox2等多能性维持基因之间的相互作用关系,并展望其应用前景。

Embryonic stem cells （ES） have the unique capacity to proliferate extensively while maintaining pluripotency. ES cell lines can also be generated from human blastocyst embryos, and are considered promising donor sources for cell transplantation therapies for diseases such as juvenile diabetes, Parkinson＇s disease, and heart failure. However, as for organ transplants, tissue rejection remains a significant concern for ES cell transplantation. Another concern is the use of human embryos. One possible means to avoid these is,sues is by reprogramming the nuclei of differentiated cells to ES cell-like, pluripotent cells. Several extrinsic signals such as LIF, BMP and Wnt can support the self-renewal and pluripotency of embryonic stem （ES） cells through regulating the ＂pluripotent genes＂. A unique homeobox transcription factor, Nanog, is one of the key downstream effectors of these signals. Elevated level of Nanog can maintain the mouse ES cell self-renewal independent of I.IF and enable human ES cell growth without feeder cells. In addition to the external signal pathways, intrinsic transcription factors such as FoxD3, P53 and Oct4 are also involved in regulating the expression of Nanog. Functionally, Nanog works together with other key pluripotent factors such as Oct4 and Sox2 to control a set of target genes that have important functions in ES cell pluripotency. These key factors form a regulatory network to support or limit each other＇s expression level, which maintains the properties of ES cells.