10月1日，中國科學(xué)院廣州生物醫(yī)藥與健康研究院干細(xì)胞與再生醫(yī)學(xué)研究所,，繼去年11月在《細(xì)胞研究》雜志發(fā)表誘導(dǎo)多能性干細(xì)胞（iPS）技術(shù)相關(guān)文章之后,，又有一篇相關(guān)論文在《生物化學(xué)雜志》（J. Biol. Chem）在線發(fā)表,。
iPS技術(shù)，即誘導(dǎo)多能性干細(xì)胞技術(shù),，是一種將分化細(xì)胞重編程為類似胚胎干細(xì)胞的新興技術(shù),，它通過病毒載體將特定轉(zhuǎn)錄因子組合轉(zhuǎn)入被誘導(dǎo)細(xì)胞，使其發(fā)生重編程,。iPS細(xì)胞具有多能性和自我更新的能力,，目前已成功獲得小鼠和人的iPS細(xì)胞。這項(xiàng)技術(shù)擁有巨大的潛在應(yīng)用價(jià)值,，利用iPS技術(shù)能夠獲得病人或疾病特異的多能性干細(xì)胞,，此外，它不僅能避免移植中的免疫排斥問題,，也繞開了人類胚胎干細(xì)胞研究帶來的倫理問題,。但iPS技術(shù)的臨床應(yīng)用之路還很漫長，有許多技術(shù)難題需要解決,，在這些問題中iPS重編程的完全性和均一性是首要問題,。
中國科學(xué)院廣州生物醫(yī)藥與健康研究院干細(xì)胞與再生醫(yī)學(xué)研究所的裴端卿教授帶領(lǐng)同事們發(fā)現(xiàn)，在小鼠腦膜（meningeal）細(xì)胞中,，重要的胚胎干細(xì)胞調(diào)控因子之一——Sox2的表達(dá)含量非常高,，而且這種細(xì)胞易于誘導(dǎo)為iPS細(xì)胞。通過DNA甲基化分析得知,，由腦膜細(xì)胞形成的iPS克隆不需要經(jīng)過篩選就能夠發(fā)生完全的重編程,，而且這些克隆能夠100%產(chǎn)生嵌合小鼠。
這項(xiàng)結(jié)果發(fā)現(xiàn)了一種可誘導(dǎo)為iPS的新型成體細(xì)胞,。在此之前的研究中,，研究者可以使用成纖維細(xì)胞（例如MEF）以及神經(jīng)干細(xì)胞進(jìn)行iPS誘導(dǎo),，由于取材困難，培養(yǎng)要求極高,，不利于大規(guī)模應(yīng)用,。而腦膜細(xì)胞克服了上述困難。這項(xiàng)研究成果為iPS技術(shù)的研究和應(yīng)用,，尤其是與腦部相關(guān)的疾病研究,，提供了一種非常有價(jià)值的研究手段和途徑。（生物谷Bioon.com）
生物谷推薦原始出處：
J. Biol. Chem,，doi:10.1074/jbc.M706009200,，Zhe Wang，Duanqing Pei
Aromatic Residues in the C-terminal Domain 2 Are Required for Nanog to Mediate LIF-independent Self-renewal of Mouse Embryonic Stem Cells
Zhe Wang, Tianhua Ma, Xiaoke Chi, and Duanqing Pei
From the Stem Cell and Cancer Biology Group, Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663, China and the Laboratory of Stem Cell Biology, Department of Biological Sciences & Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institutes of Biomedicine, School of Medicine, Tsinghua University, Beijing 100084, China
Nanog was identified by its ability to sustain the LIF-independent self-renewal of mouse embryonic stem (ES) cells and has recently been shown to play a role in reprogramming adult fibroblasts into pluripotent stem cells. However, little is known about the structural basis of these remarkable activities of Nanog. We have previously identified an unusually strong transactivator named CD2 at its C terminus. Here we demonstrate that CD2 is required for Nanog to mediate ES cell self-renewal. Furthermore, deletion and point mutation analysis revealed that CD2 relies on at least seven aromatic amino acid residues to generate its potent transactivating activity. A mutant Nanog bearing alanine substitutions for these seven residues fails to confer LIF-independent self-renewal in mouse ES cells. Substitution of CD2 by the viral transactivator VP16 gave rise to Nanog-VP16, which is 10 times more active than wild-type Nanog in ES cells. Surprisingly, the expression of Nanog-VP16 in mouse ES cells induces differentiation and is thus unable to sustain LIF-independent self-renewal for mouse ES cells. Taken together, our results demonstrate that the CD2 domain of Nanog is a unique transactivator that utilizes aromatic residues to confer specific activity absolutely required for ES self-renewal.
