Regenerative Bioscience Center, University of Georgia, Athens, Georgia, United States of America.
PLoS One. 2011;6(8):e23266. doi: 10.1371/journal.pone.0023266. Epub 2011 Aug 5.
Human embryonic stem cells (hESCs) and their differentiated progeny allow for investigation of important changes/events during normal embryonic development. Currently most of the research is focused on proteinacous changes occurring as a result of differentiation of stem cells and little is known about changes in cell surface glycosylation patterns. Identification of cell lineage specific glycans can help in understanding their role in maintenance, proliferation and differentiation. Furthermore, these glycans can serve as markers for isolation of homogenous populations of cells. Using a panel of eight biotinylated lectins, the glycan expression of hESCs, hESCs-derived human neural progenitors (hNP) cells, and hESCs-derived mesenchymal progenitor (hMP) cells was investigated. Our goal was to identify glycans that are unique for hNP cells and use the corresponding lectins for cell isolation. Flow cytometry and immunocytochemistry were used to determine expression and localization of glycans, respectively, in each cell type. These results show that the glycan expression changes upon differentiation of hESCs and is different for neural and mesenchymal lineage. For example, binding of PHA-L lectin is low in hESCs (14±4.4%) but significantly higher in differentiated hNP cells (99±0.4%) and hMP cells (90±3%). Three lectins: VVA, DBA and LTL have low binding in hESCs and hMP cells, but significantly higher binding in hNP cells. Finally, VVA lectin binding was used to isolate hNP cells from a mixed population of hESCs, hNP cells and hMP cells. This is the first report that compares glycan expression across these human stem cell lineages and identifies significant differences. Also, this is the first study that uses VVA lectin for isolation for human neural progenitor cells.
人类胚胎干细胞(hESCs)及其分化后代可用于研究正常胚胎发育过程中的重要变化/事件。目前,大多数研究都集中在干细胞分化过程中发生的蛋白质变化上,而对于细胞表面糖基化模式的变化知之甚少。鉴定细胞谱系特异性聚糖有助于了解其在维持、增殖和分化中的作用。此外,这些聚糖可以作为分离同质细胞群体的标志物。本研究使用了一组八种生物素化的凝集素来研究 hESCs、hESCs 衍生的人类神经祖细胞(hNP)细胞和 hESCs 衍生的间充质祖细胞(hMP)的聚糖表达。我们的目标是鉴定 hNP 细胞特有的聚糖,并使用相应的凝集素来进行细胞分离。流式细胞术和免疫细胞化学分别用于确定每种细胞类型中聚糖的表达和定位。这些结果表明,hESCs 分化后糖基化表达发生变化,且在神经和间充质谱系中存在差异。例如,PHA-L 凝集素的结合在 hESCs 中较低(14±4.4%),但在分化的 hNP 细胞(99±0.4%)和 hMP 细胞(90±3%)中显著升高。三种凝集素:VVA、DBA 和 LTL 在 hESCs 和 hMP 细胞中的结合较低,但在 hNP 细胞中的结合显著升高。最后,使用 VVA 凝集素从 hESCs、hNP 细胞和 hMP 细胞的混合群体中分离 hNP 细胞。这是首次比较这些人类干细胞谱系中的聚糖表达并鉴定出显著差异的报告。此外,这是首次使用 VVA 凝集素分离人类神经祖细胞的研究。