JBC：碳水化合物能调控干细胞潜能

Shoko Ni…

硫酸乙酰肝素（Heparan sulfate）是一种碳水化合物分子，它是细胞表面某些蛋白质的包被物，有研究者报道，这种化合物对胚胎干细胞的正常增殖和潜能非常重要。

正是由于干细胞有不断的自我更新以及分化为各种成体细胞的能力才使它们拥有巨大的治疗潜力。研究者们一直希望揭示干细胞具有这些能力的原理，已经知道有若干蛋白质和生长因子在细胞内外起重要作用，但其分子机制基本还属于未知范畴。

很多干细胞相关因子都会与硫酸乙酰肝素分子相结合，因此Shoko Nishihara及其同事们检测了减少或阻断硫酸乙酰肝素对培养的小鼠干细胞产生的影响。

他们发现，缺少HS时，促进干细胞更新的三种主要细胞外因子（名为Wnt、FGF和BMP的蛋白质）无法正确的向细胞内传递信号。

因此，缺少HS的细胞生长缓慢，并且往往会自动分化为其他细胞，分化的比率和HS被抑制的程度相关。Nishihara及其同事认为，硫酸乙酰肝素可能是介导细胞内外促使干细胞更新信号的细胞表面元件，它有可能成为干细胞工程的重要靶标。相关论文发表于2008年2月8日《生物化学杂志》（JBC）上。（来源：中科院广州生物医药与健康研究院）

（《生物化学杂志》（JBC），Vol. 283, Issue 6, 3594-3606，Norihiko Sasaki，Shoko Nishihara）

生物谷推荐原始出处：

Originally published In Press as doi:10.1074/jbc.M705621200 on November 16, 2007

J. Biol. Chem., Vol. 283, Issue 6, 3594-3606, February 8, 2008

Heparan Sulfate Regulates Self-renewal and Pluripotency of Embryonic Stem Cells*

Norihiko Sasaki ${ddagger}$ $§$ , Kazuhiko Okishio ${ddagger}$ , Kumiko Ui-Tei¶, Kaoru Saigo¶, Akiko Kinoshita-Toyoda $§$ ||, Hidenao Toyoda $§$ ||, Tomoaki Nishimura** ${ddagger}$ ${ddagger}$ , Yasuo Suda $§$ ** ${ddagger}$ ${ddagger}$ , Michiko Hayasaka $§$ $§$ , Kazunari Hanaoka $§$ $§$ , Seiji Hitoshi¶¶, Kazuhiro Ikenaka¶¶, and Shoko Nishihara ${ddagger}$ $§$ 1

From the ${ddagger}$ Laboratory of Cell Biology, Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577, the ¶Department of Biophysics and Biochemistry, Graduate School of Science, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, the ||Department of Bioanalytical Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, the **Department of Nanostructure and Advanced Materials, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Kohrimoto, Kagoshima 890-0065, ${ddagger}$ ${ddagger}$ Sudx-Biotec Corporation, KIBC 461, 5-5-2, Minatojima-minami, Chuo-ku, Kobe 650-0047, $§$ $§$ Laboratory of Molecular Embryology, Department of Bioscience, Kitasato University School of Science, 1-15-1 Kitasato, Sagamihara, Kanagawa 228, ¶¶Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, 38 Nishigonaka Myodaiji, Okazaki, Aichi 444-8585, and $§$ Core Research for Evolutional Science and Technology of Japan Science and Technology Agency, Kawaguchi Center Building, 4-1-8, Hon-cho, Kawaguchi, Saitama 332-0012, Japan

Embryonic stem (ES) cell self-renewal and pluripotency are maintained by several signaling cascades and by expression of intrinsic factors, such as Oct3/4 and Nanog. The signaling cascades are activated by extrinsic factors, such as leukemia inhibitory factor, bone morphogenic protein, and Wnt. However, the mechanism that regulates extrinsic signaling in ES cells is unknown. Heparan sulfate (HS) chains are ubiquitously present as the cell surface proteoglycans and are known to play crucial roles in regulating several signaling pathways. Here we investigated whether HS chains on ES cells are involved in regulating signaling pathways that are important for the maintenance of ES cells. RNA interference-mediated knockdown of HS chain elongation inhibited mouse ES cell self-renewal and induced spontaneous differentiation of the cells into extraembryonic endoderm. Furthermore, autocrine/paracrine Wnt/β-catenin signaling through HS chains was found to be required for the regulation of Nanog expression. We propose that HS chains are important for the extrinsic signaling required for mouse ES cell self-renewal and pluripotency.