Cell:生长因子环境决定干细胞基态

http://www.microimage.com.cn未知(2008-11-05 13:40:47)

(封面图片:Yu-Fen Chou等科学家发现多能干细胞存在多个基态,每一个基态都具有自身独特的分子和生物学特性。在封面图中,作者用不同色彩的环表示不同的干细胞状态,这些环互相联结。细胞能从一个态转化为下一个确定的态,这导致了世系分化以及胚胎发生,以上过程通过中间的胚胎辐射出的路径表达。)

干细胞具有多能性,这是一种维持细胞自我更新以及产生三胚层衍生组织的能力。长久以来科学家们一直认为,干细胞多能性是一种单一的高阶基态,并且随着细胞分化的开始而逐步丧失。而在2008年10月31日出版的《细胞》(Cell)上,来自美国麻省综合医院的Yu-Fen Chou等科学家认为,事实上存在多个这样的基态,每一个基态都具有自身独特的分子和生物学特性。

在本期的封面文章中,研究小组证明了干细胞能从一个态转化到另一个态,而以上过程很大程度上取决于细胞生长因子微环境。多能干细胞系(pluripotent stem cell line)能由囊胚产生,这一部分最终得到胚胎干细胞系(embryonic stem cell line,ES cell line),而另一部分多能干细胞来自于上胚层,这部分最终得到上胚层干细胞系(epiblast stem cell line,EpiSCs line)。而ES细胞以及EpiSCs细胞在结合维持其多能状态的生长因子时表现出极大的差异。这两种干细胞种类的分子以及功能上的差别证明,组织来源和生长因子环境或许对于决定干细胞类型非常重要。

此外,科学家研究了组织来源以及生长因子是如何影响干细胞多能状态的。研究小组证实能从小鼠囊胚得到具有独特功能和分子特性的新干细胞系,并且生长因子培养环境和细胞间相互作用在确定独特且稳定的干细胞基态方面具有至关重要的作用。(

原始出处:

Cell,Volume 135, Issue 3, 449-461, 31 October 2008,Yu-Fen Chou, Niels Geijsen

The Growth Factor Environment Defines Distinct Pluripotent Ground States in Novel Blastocyst-Derived Stem Cells

Yu-Fen Chou1,7,Hsu-Hsin Chen1,7,Maureen Eijpe2,7,Akiko Yabuuchi3,Joshua G. Chenoweth4,Paul Tesar5,Jun Lu6,Ronald D.G. McKay4andNiels Geijsen1,,

1 Harvard Stem Cell Institute, Massachusetts General Hospital, Center for Regenerative Medicine, CPZN  4256, 185 Cambridge Street, Boston, MA 02114, USA
2 Erasmus Medical Centre, Department of Cell Biology, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands
3 Division of Pediatric Hematology/Oncology, Children's Hospital Boston, One Blackfan Circle, Boston, MA, 02115, USA
4 Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
5 Department of Genetics, Case Western Reserve University, 2109 Adelbert Road BRB-725, Cleveland, OH 44106, USA
6 The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02141, USA
7 These authors contributed equally to this work

SUMMARY

Pluripotent stem cell lines can be derived from blastocyst embryos, which yield embryonic stem cell lines (ES cells), as well as the postimplantation epiblast, which gives rise to epiblast stem cell lines (EpiSCs). Remarkably, ES cells and EpiSCs display profound differences in the combination of growth factors that maintain their pluripotent state. Molecular and functional differences between these two stem cell types demonstrate that the tissue of origin and/or the growth factor milieu may be important determinants of the stem cell identity. We explored how developmental stage of the tissue of origin and culture growth factor conditions affect the stem cell pluripotent state. Our findings indicate that novel stem cell lines, with unique functional and molecular properties, can be generated from murine blastocyst embryos. We demonstrate that the culture growth factor environment and cell-cell interaction play a critical role in defining several unique and stable stem cell ground states.

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