南加大(University of Southern California)的研究人员发现称为IQ-1的小分子，在预防胚胎干细胞分化成特殊细胞的过程中扮演相当关键的角色。此研究刚发表于PNAS在线期刊。Michael Kahn 博士说：这项发现提供研究人员另一个方法，使胚胎干细胞能处于未分化的状态。过去比较典型的策略是利用老鼠饲养层(mouse feeder layer，简称MFL)的纤维母细胞来抑制胚胎干细胞的分化，使胚胎干细胞能一代一代的继代下去。
    但是，使用MFL常发现会有醣蛋白(glycoproteins)污染的问题，若在人类胚胎干细胞中使用，则会有大量免疫反应的发生。也因此需要开发新的方法来解决MFL所产生的问题，而IQ-1的发现则提供另一个极有潜力的选择。IQ-1主要能阻断细胞内Wnt的讯息传递路径(Wnt signal pathway)，而Wnt路径主要的功能是负责干细胞的增生(proliferation)及分化(differentiation)。更仔细来说，IQ-1是阻断p300蛋白，以避免其与s-catenin结合，这样就能阻止干细胞的分化作用，同时，IQ-1还能增加CBP蛋白与s-catenin的结合作用，使干细胞能继续以原态进行分裂增生。
    目前IQ-1已用于老鼠胚胎干细胞与人类胚胎干细胞的测试，两个系统中IQ-1抑制干细胞分化的效果都类似。Kahn表示：「假如以化学法就能抑制干细胞的分化，就可以排除掉许多污染的问题，这样一来科学家处理干细胞就能更得心应手了。」先前Kahn研究团队也已研发出另一种化合物，能大量的增殖纯的胚胎干细胞，这些技术都是研发干细胞治疗法的基本要件。因此，在干细胞研究领域中具有很重要的贡献。
     (资料来源 : Bio.com)
英文原文：
USC Researchers Have Discovered a Small Molecule That May Allow for Growth of Human Stem Cells Without Threat of Contamination
 

03/21/07 -- A newly discovered small molecule called IQ-1 plays a key role in preventing embryonic stem cells from differentiating into one or more specific cell types, allowing them to instead continue growing and dividing indefinitely, according to research performed by a team of scientists who recently have joined the stem cell research efforts at the Keck School of Medicine of USC.
Their findings are published today in an early online edition of the Proceedings of the National Academy of Sciences.
This discovery takes scientists another step closer to being able to grow embryonic stem cells without the ?feeder layer? of mouse fibroblast cells that is essential for maintaining the potency of embryonic stem cells, said Michael Kahn, the study?s primary investigator who recently was named the first Provost?s Professor of Medicine and Pharmacy at USC.
Such a layer is needed because it is currently the only proven method to provide the stem cells with the necessary chemical signals that prompt them to stay undifferentiated and to continue dividing over and over.
Still, growing human embryonic stem cells on a layer of mouse fibroblasts has never made much sense to the scientists forced to do just that.
?Stem cells that grow on feeders are contaminated with mouse glycoproteins markers,? Kahn said. ?If you use them in humans, you?d potentially have a horrible immune response.?
And so, in order to take any eventual stem cell-based treatments from the laboratory to the clinic, there needs to be a way to keep the cells growing and dividing without the use of mouse fibroblasts. The discovery of IQ-1, Kahn said, is a significant step in that direction.
What IQ-1 does, he explained, is to block one arm of a cell-signaling pathway called the Wnt pathway, while enhancing the signal coming from the other arm of the Wnt pathway. The Wnt pathway is known to have dichotomous effects on stem cells, both proliferative and differentiative.
More specifically, IQ-1 blocks the coactivator p300 from interacting with the protein ?-catenin; this prevents the stem cells from being ?told? to differentiate into a more specific cell type. At the same time, IQ-1 enhances the interaction between the coactivator CBP and ?-catenin, which signals the cells to keep dividing and to remain as fully potent stem cells.
?This way, you can essentially maintain the stem cell?s growth and potency for as long as you want,? Kahn said.
The studies of IQ-1 and its effects reported in the newly published PNAS paper were performed at the University of Washington by Kahn and his colleagues (along with collaborators from the Asahi Kasei Corp. in Shizuoka, Japan) using mouse embryonic stem cells. But Kahn noted that subsequent pilot studies using human embryonic stem cells, in collaboration with Qilong Ying at the Center for Stem Cell and Regenerative Medicine at the Keck School of Medicine, have confirmed that IQ-1 plays a similar role in that system as well.
?If we can create a totally chemically defined system for growing human embryonic stem cells without any risk of contamination, it would make life much easier for scientists than it is at the moment,? Kahn said. ?And that?s our goal.?
Martin Pera, director of the Center for Stem Cell and Regenerative Medicine at the Keck School of Medicine, said, ?Kahn's study provides us with striking new insights into the molecular regulatory machinery inside embryonic stem cells. His team has identified a chemical that controls a critical switch that enables stem cells to multiply indefinitely in the laboratory. These findings will help lead to the development of new techniques to propagate pure populations of embryonic stem cells on a large scale, an essential prerequisite to the successful development of stem cell-based therapies.
Source: University of Southern California

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