Heparan sulfate regulates self-renewal and pluripotency of embryonic stem cells
Heparan sulfate regulates self-renewal and pluripotency of embryonic stem cells
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DOI：
10.1074/jbc.m705621200
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发表时间：
2008-02-08
影响因子：
4.8
通讯作者：
Nishihara, Shoko
中科院分区：
文献类型：
--
作者：
Sasaki, Norihiko;Okishio, Kazuhiko;Nishihara, Shoko
胚胎干细胞（ES）的自我更新和多能性是由几个信号级联和表达的内在因素，如Oct 3/4和Nanog。信号级联被外在因素激活，如白血病抑制因子、骨形态发生蛋白和Wnt。然而，调节ES细胞中外源性信号传导的机制尚不清楚。硫酸乙酰肝素（HS）链作为细胞表面蛋白聚糖普遍存在，并且已知在调节几种信号传导途径中起关键作用。在这里，我们研究了ES细胞上的HS链是否参与调节对维持ES细胞很重要的信号通路。RNA干扰介导的HS链延长的敲低抑制小鼠ES细胞自我更新，并诱导细胞自发分化为胚外内胚层。此外，发现通过HS链的自分泌/旁分泌Wnt/β-连环蛋白信号传导对于Nanog表达的调节是必需的。我们认为HS链对于小鼠ES细胞自我更新和多能性所需的外在信号传导是重要的。
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/beta-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.