Glycome profiling by lectin microarray reveals dynamic glycan alterations during epidermal stem cell aging
Glycome profiling by lectin microarray reveals dynamic glycan alterations during epidermal stem cell aging
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DOI：
10.1111/acel.13190
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发表时间：
2020-07-18
期刊：
影响因子：
7.8
通讯作者：
Yanagisawa, Hiromi
中科院分区：
文献类型：
--
作者：
Oinam, Lalhaba;Changarathil, Gopakumar;Yanagisawa, Hiromi
表皮老化的特点是屏障功能逐渐下降、伤口愈合受损、脱发和患癌症的风险增加。这可能是由于表皮干细胞特性与年龄相关的变化以及与其微环境的相互作用缺陷所致。目前，还没有生化工具可以检测和评估表皮干细胞的衰老情况。细胞糖基化参与各种生理和病理条件下的细胞间通讯和细胞基质粘附。在这里，我们探索了表皮干细胞中聚糖的变化作为潜在的衰老生物标志物。使用凝集素微阵列，我们对年轻和年老小鼠皮肤中新鲜分离的表皮干细胞进行了全面的聚糖分析。年轻和年老小鼠的表皮干细胞在聚糖谱上表现出显着差异。特别是，在老表皮干细胞中，甘露糖结合剂 rHeltuba 的结合减少，而 α 2-3Sia 结合剂 rGal8N 的结合增加。这些聚糖变化伴随着老表皮干细胞中唾液酸转移酶、St3gal2和St6gal1以及甘露糖苷酶Man1基因的上调。通过过度表达这些糖原来修饰细胞表面聚糖会导致培养中的表皮干细胞的再生能力缺陷。因此，我们的研究表明细胞糖基化模式与年龄相关的整体改变及其对干细胞功能的潜在贡献。凝集素检测到的这些聚糖修饰可能作为衰老的分子标记，进一步的功能研究将使我们更好地了解皮肤衰老的过程。
Aging in the epidermis is marked by a gradual decline in barrier function, impaired wound healing, hair loss, and an increased risk of cancer. This could be due to age-related changes in the properties of epidermal stem cells and defective interactions with their microenvironment. Currently, no biochemical tools are available to detect and evaluate the aging of epidermal stem cells. The cellular glycosylation is involved in cell-cell communications and cell-matrix adhesions in various physiological and pathological conditions. Here, we explored the changes of glycans in epidermal stem cells as a potential biomarker of aging. Using lectin microarray, we performed a comprehensive glycan profiling of freshly isolated epidermal stem cells from young and old mouse skin. Epidermal stem cells exhibited a significant difference in glycan profiles between young and old mice. In particular, the binding of a mannose-binder rHeltuba was decreased in old epidermal stem cells, whereas that of an alpha 2-3Sia-binder rGal8N increased. These glycan changes were accompanied by upregulation of sialyltransferase,St3gal2andSt6gal1and mannosidaseMan1agenes in old epidermal stem cells. The modification of cell surface glycans by overexpressing these glycogenes leads to a defect in the regenerative ability of epidermal stem cells in culture. Hence, our study suggests the age-related global alterations in cellular glycosylation patterns and its potential contribution to the stem cell function. These glycan modifications detected by lectins may serve as molecular markers for aging, and further functional studies will lead us to a better understanding of the process of skin aging.