王剑龙《自然》文章：胚胎干细胞蛋白图谱

　　

生物通报道：来自哈佛医学院干细胞研究所，Dana-Farber癌症研究所和波士顿儿童医院（Dana-Farber Cancer Institute，Children's Hospital Boston），以及霍德华休斯医学院HHIMI的研究人员绘制了一张小鼠胚胎干细胞全能性Nanog蛋白相互作用图谱，为干细胞研究以及全能性干细胞的应用提供了重要资料。这一研究成果公布11月16日《Nature》杂志上。

哈佛医学院干细胞研究所(Harvard Stem Cell Institute）是一所著名的科学研究机构，其宗旨是将干细胞生物学研究建立成疾病治疗的基础。这一研究报告就是出自哈佛干细胞研究所，文章的第一作者是就读于该所的王剑龙博士（Jianlong Wang，音译）

链接：
Nature 444, 364-368 (16 November 2006) | 
doi:10.1038/nature05284; Received 10 April 2006; Accepted 27 September 2006; Published online 8 November 2006
A protein interaction network for pluripotency of embryonic stem cells
[Abstract]

干细胞是指那些同时具有自我更新和产生分化细胞能力的细胞。尤其在早期胚胎发生过程中，它们可以产生构成身体器官各种类型的组织。这种细胞就是胚胎干细胞（Embryonic stem，ES），发育生物学家将它们称为“全能性细胞”。

胚胎干细胞是当今生命科学和生物技术研究的热点，这主要是由于其具有“发育全能性”的功能。ES能分化成人体200多种细胞类型，形成机体的任何细胞、组织和器官。通过掌握其分化发育的规律，在人工条件下定向分化为所需的细胞、组织乃至器官，科学家们希望可以用来治疗目前还难以或无法治愈的帕金森氏病、早老性痴呆、白血病、糖尿病等顽症，并且解决十分紧缺的组织和器官移植的来源问题，并且通过进一步与克隆技术相结合，运用体细胞核转移技术来得到ES，还能解决细胞治疗以及组织和器官移植的免疫排异难题。

利用细胞融合（核移植），体细胞可以获得胚胎细胞的这些表型，这个过程是通过一个同源域(homeodomain)蛋白：Nanog蛋白调控的——Nanog蛋白在ES细胞全能性维持方面起着关键作用：今年10月的一篇报道中，英国皇家科学院院士Austin Smith教授和同事发现转录因子Nanog是调控着细胞融合后的多重功能的关键因子。

在这篇研究报告中，Wang等人研究获得了小时胚胎干细胞中Nanog调控的蛋白网络图谱，实验手段主要是通过在天然条件下亲和纯化Nanog蛋白，然后进行质谱分析，从而确认了相关蛋白的物理图谱。几次实验之后研究人员辨认了几个Nanag相关蛋白的伴侣蛋白（包括Oct4），增加了新筛选得到的蛋白因子的功能相关性，从而构建了一张蛋白相互作用图谱。

这张图谱包含了许多在维持胚胎干细胞和调控分化方面的核心因子，也与其它一些复合共抑制途径（multiple co-repressor pathways）相关，其中许多蛋白的编码基因是之前假设的直接转录靶标。这一相互作用密切的蛋白图谱可以说就是一个全能性作用的细胞模型。（生物通：张迪）

附:

哈佛干细胞研究员研究综述
Stem cells are the source of all tissues of the body. Harnessing the potential of these cells may make it possible to develop new treatments for many diseases by replacing cells that are lost or damaged in the disease process. Transplants of bone marrow stem cells are already in widespread use and have saved countless thousands of lives. Future candidates for cell replacement therapy include the insulin-producing cells that are lost in type I diabetes, the midbrain dopamine neurons that degenerate in Parkinson's disease, and the myocardial cells that are lost following a heart attack.

Some organs contain stem cells that persist throughout adult life; they contribute to the maintenance or repair of those organs. However, not every organ has been shown to contain stem cells, and in general adult stem cells appear to have restricted developmental potential; they have only limited capacity for proliferation and can give rise only to a few cell types. In contrast, embryonic stem (ES) cells can divide almost indefinitely and can give rise to every cell type in the body, suggesting that they may be the most versatile source of cells for transplantation therapy.

The first human ES cells were derived from surplus embryos generated during in vitro fertilization (IVF) treatment. More recently, however, the technique of somatic cell nuclear transfer into unfertilized eggs offers the possibility of creating human ES cells whose genetic makeup matches that of the donor. In addition to providing a powerful research tool for understanding human disease, this approach may eventually allow patients to be treated with an unlimited supply of new cells that will be recognized as 'self,' thereby avoiding the serious problem of rejection by the body's own immune defenses.

As an alternative to transplantation therapy, it may also be possible in some cases to stimulate the adult stem cells that already exist within a damaged organ or tissue using growth factors or other agents; essentially, this approach is effectively a way of harnessing the body's own repair mechanisms to accelerate healing. To achieve this goal, we will need to discover much more about the natural biology of the different types of stem cells and to understand their actual and potential abilities to repair different types of damage.

The Harvard Stem Cell Institute ( HSCI ) is committed to exploring all of these approaches, including both embryonic and adult stem cells. Our overall aim is to bring stem cells to the clinic as quickly as possible for as many different diseases as possible. Achieving this will require advances on many levels, from basic biology to patient delivery systems. The Harvard community, comprising the university, the medical school, and 18 hospitals and research institutions, is one of the largest concentrations of biomedical researchers in the world and is well positioned to make this vision a reality.