Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
J Histochem Cytochem. 2012 Dec;60(12):943-9. doi: 10.1369/0022155412465090. Epub 2012 Oct 4.
Embryonic stem (ES) cells are derived from the inner cell mass of the blastocyst and can give rise to all cell types in the body. The fate of ES cells depends on the signals they receive from their surrounding environment, which either promote self-renewal or initiate differentiation. Heparan sulfate proteoglycans are macromolecules found on the cell surface and in the extracellular matrix. Acting as low-affinity receptors on the cell surface, heparan sulfate (HS) side chains modulate the functions of numerous growth factors and morphogens, having wide impact on the extracellular information received by cells. ES cells lacking HS fail to differentiate but can be induced to do so by adding heparin. ES cells defective in various components of the HS biosynthesis machinery, thus expressing differently flawed HS, exhibit lineage-specific effects. Here we discuss recent studies on the biological functions of HS in ES cell developmental processes. Since ES cells have significant potential applications in tissue/cell engineering for cell replacement therapies, understanding the functional mechanisms of HS in manipulating ES cell growth in vitro is of utmost importance, if the stem cell regenerative medicine from scientific fiction ever will be made real.
胚胎干细胞(ES 细胞)来源于囊胚的内细胞团,能够分化为体内所有类型的细胞。ES 细胞的命运取决于它们从周围环境中接收到的信号,这些信号促进自我更新或启动分化。硫酸乙酰肝素蛋白聚糖是细胞表面和细胞外基质中发现的大分子。作为细胞表面的低亲和力受体,硫酸乙酰肝素(HS)侧链调节许多生长因子和形态发生素的功能,对细胞接收到的细胞外信息产生广泛影响。缺乏 HS 的 ES 细胞无法分化,但通过添加肝素可以诱导其分化。HS 生物合成机制的各种成分有缺陷的 ES 细胞,因此表达不同缺陷的 HS,表现出谱系特异性的影响。在这里,我们讨论了 HS 在 ES 细胞发育过程中的生物学功能的最新研究。由于 ES 细胞在组织/细胞工程中的细胞替代疗法中有重要的应用前景,因此了解 HS 在体外操纵 ES 细胞生长的功能机制非常重要,如果科学幻想中的干细胞再生医学能成为现实的话。