Nature：人类的胚胎干细胞是生命能量的“永久发动机”
生物谷：一组人类胚胎干细胞正在制造类似胰岛素的生长因子(IGF)受体(红色部分),周围的壁龛细胞正在制造类似纤维原细胞的生长因子(FGF)受体(绿色部分)。蓝色部分代表所有细胞的细胞核。
科学家将人类胚胎干细胞在机体组织中的小生物环境称为壁龛(niche)，它对干细胞有重要影响。加拿大科学家最近发现，壁龛的作用比原来已知的更加复杂，人类胚胎干细胞其实是生命能量的“永久发动机”。
在7月11日的《自然》在线上，加拿大麦克马斯特癌症与干细胞研究所(McMaster Cancer and Stem Cell Research Institute)的研究人员报告说，胚胎干细胞可以制造特别的壁龛细胞，然后这些壁龛细胞会释放干细胞所需的蛋白质，保证这些“母体”平稳运行。
Mick Bhatia等人首次证实，即使在体外，人类胚胎干细胞也拥有产生类似纤维原细胞的壁龛细胞hdFs的能力，这些hfFs会不断制造有用的蛋白质，包括类似胰岛素的2号生长因子(IGF-II)，研究人员认为，IGF-II很可能正是维持人类胚胎干细胞所需的那种蛋白质。
研究人员之所以对干细胞与壁龛的关系非常感兴趣，是因为壁龛显示了控制干细胞行为的一种途径，也就是说，如果人类能够控制胚胎干细胞的某些分化方向，那么将有可能找到修复破损组织的再生疗法，如修复帕金森症的神经元或者糖尿病中的胰岛素制造细胞。(中国科学技术信息研究所加工整理)
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Nature advance online publication 11 July 2007 | doi:10.1038/nature06027; Received 24 April 2007; Accepted 18 June 2007; Published online 11 July 2007
IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro
Sean C. Bendall1,2,3, Morag H. Stewart1,3, Pablo Menendez1,4, Dustin George2, Kausalia Vijayaragavan1, Tamra Werbowetski-Ogilvie1, Veronica Ramos-Mejia1, Anne Rouleau1, Jiabi Yang1, Marc Bossé1, Gilles Lajoie2 & Mickie Bhatia1
- McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, and Department of Biochemistry, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
- Don Rix Protein Identification Facility, Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
- These authors contributed equally to this work.
- Present address: Spanish Stem Cell Bank-Andalucian Branch, Instituto de Investigaciones Biomedicas, Granada 18100, Spain.
Correspondence to: Mickie Bhatia1 Correspondence and requests for materials should be addressed to M.B. (Email: mbhatia@mcmaster.ca).
Distinctive properties of stem cells are not autonomously achieved, and recent evidence points to a level of external control from the microenvironment. Here, we demonstrate that self-renewal and pluripotent properties of human embryonic stem (ES) cells depend on a dynamic interplay between human ES cells and autologously derived human ES cell fibroblast-like cells (hdFs). Human ES cells and hdFs are uniquely defined by insulin-like growth factor (IGF)- and fibroblast growth factor (FGF)-dependence. IGF 1 receptor (IGF1R) expression was exclusive to the human ES cells, whereas FGF receptor 1 (FGFR1) expression was restricted to surrounding hdFs. Blocking the IGF-II/IGF1R pathway reduced survival and clonogenicity of human ES cells, whereas inhibition of the FGF pathway indirectly caused differentiation. IGF-II is expressed by hdFs in response to FGF, and alone was sufficient in maintaining human ES cell cultures. Our study demonstrates a direct role of the IGF-II/IGF1R axis on human ES cell physiology and establishes that hdFs produced by human ES cells themselves define the stem cell niche of pluripotent human stem cells.
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