10月1日，中国科学院广州生物医药与健康研究院干细胞与再生医学研究所，继去年11月在《细胞研究》杂志发表诱导多能性干细胞（iPS）技术相关文章之后，又有一篇相关论文在《生物化学杂志》（J. Biol. Chem）在线发表。
iPS技术，即诱导多能性干细胞技术，是一种将分化细胞重编程为类似胚胎干细胞的新兴技术，它通过病毒载体将特定转录因子组合转入被诱导细胞，使其发生重编程。iPS细胞具有多能性和自我更新的能力，目前已成功获得小鼠和人的iPS细胞。这项技术拥有巨大的潜在应用价值，利用iPS技术能够获得病人或疾病特异的多能性干细胞，此外，它不仅能避免移植中的免疫排斥问题，也绕开了人类胚胎干细胞研究带来的伦理问题。但iPS技术的临床应用之路还很漫长，有许多技术难题需要解决，在这些问题中iPS重编程的完全性和均一性是首要问题。
中国科学院广州生物医药与健康研究院干细胞与再生医学研究所的裴端卿教授带领同事们发现，在小鼠脑膜（meningeal）细胞中，重要的胚胎干细胞调控因子之一——Sox2的表达含量非常高，而且这种细胞易于诱导为iPS细胞。通过DNA甲基化分析得知，由脑膜细胞形成的iPS克隆不需要经过筛选就能够发生完全的重编程，而且这些克隆能够100%产生嵌合小鼠。
这项结果发现了一种可诱导为iPS的新型成体细胞。在此之前的研究中，研究者可以使用成纤维细胞（例如MEF）以及神经干细胞进行iPS诱导，由于取材困难，培养要求极高，不利于大规模应用。而脑膜细胞克服了上述困难。这项研究成果为iPS技术的研究和应用，尤其是与脑部相关的疾病研究，提供了一种非常有价值的研究手段和途径。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
