Heparan sulfate: a key regulator of embryonic stem cell fate.
Heparan sulfate: a key regulator of embryonic stem cell fate.
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DOI：
10.1515/hsz-2012-0353
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发表时间：
2013-06
影响因子：
3.7
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Kraushaar DC;Dalton S;Wang L
硫酸乙酰肝素(HS)属于糖胺多糖的一类，是一种高度硫酸盐化的线性多糖。HS的生物合成和修饰涉及多种酶。HS以糖蛋白形式存在，称为HS蛋白多糖，在细胞表面和细胞外基质中大量表达。HS与许多蛋白质相互作用，包括生长因子、形态因子和黏附分子，从而调节无脊椎动物和脊椎动物的重要发育过程。胚胎干细胞(ESCs)具有自我更新和多能性的特点。自我更新允许胚胎干细胞在其未分化状态下无限增殖，而多能性意味着它们有能力分化为三个胚层，并最终分化为成人身体的所有细胞类型。这两个特征都受到众多细胞信号通路的严格调控。最近的研究强调了HS在调节ESC功能中的重要性，特别是它们的谱系命运。在这里，我们综述了目前在理解HS在胚胎干细胞分化过程中的结构变化以及破译HS调控细胞命运的分子机制方面取得的进展。最后，我们讨论了肝素类化合物和HS生物合成的化学抑制剂在ESC培养和定向分化中的应用。
Heparan sulfate (HS) belongs to a class of glycosaminoglycans and is a highly sulfated, linear polysaccharide. HS biosynthesis and modification involves numerous enzymes. HS exists as part of glycoproteins named HS proteoglycans, which are expressed abundantly on the cell surface and in the extracellular matrix. HS interacts with numerous proteins, including growth factors, morphogens, and adhesion molecules, and thereby regulates important developmental processes in invertebrates and vertebrates. Embryonic stem cells (ESCs) are distinguished by their characteristics of self-renewal and pluripotency. Self-renewal allows ESCs to proliferate indefinitely in their undifferentiated state, whereas pluripotency implies their capacity to differentiate into the three germ layers and ultimately all cell types of the adult body. Both traits are tightly regulated by numerous cell signaling pathways. Recent studies have highlighted the importance of HS in the modulation of ESC functions, specifically their lineage fate. Here, we review the current advances that have been made in understanding the structural changes of HS during ESC differentiation and in deciphering the molecular mechanisms by which HS modulates cell fate. Finally, we discuss the applications of heparinoids and chemical inhibitors of HS biosynthesis for the manipulation of ESC culture and directed differentiation.
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影响因子：
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作者：
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DOI：
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