Glycosyltransferase ST6GAL1 contributes to the regulation of pluripotency in human pluripotent stem cells.
Glycosyltransferase ST6GAL1 contributes to the regulation of pluripotency in human pluripotent stem cells.
复制标题
DOI：
10.1038/srep13317
复制
发表时间：
2015-08-25
影响因子：
4.6
通讯作者：
Loring JF
中科院分区：
文献类型：
--
作者：
Wang YC;Stein JW;Lynch CL;Tran HT;Lee CY;Coleman R;Hatch A;Antontsev VG;Chy HS;O'Brien CM;Murthy SK;Laslett AL;Peterson SE;Loring JF
许多研究表明，糖基转移酶介导的大分子糖基化在人多能干细胞（hPSC）多能状态的调控中具有重要意义。在这里，我们观察到唾液酸转移酶ST 6 GAL 1与非多能细胞相比优先在未分化的hPSC中表达。优先识别α-2，6唾液酸化半乳糖苷的凝集素显示出与未分化的hPSC及其糖蛋白的强结合反应性，并且与分化的细胞的结合程度低得多。此外，ST 6 GAL 1在未分化hPSC中的下调导致POU 5 F1（也称为OCT 4）蛋白的减少，并显著改变了在分化期间协调细胞形态发生的许多基因的表达。体细胞中细胞多能性的诱导基本上被ST 6 GAL 1的shRNA介导的抑制所阻碍，部分地通过干扰内源性POU 5 F1和SOX 2的表达。在细胞重编程期间用唾液酸转移酶抑制剂靶向ST 6 GAL 1活性导致人诱导多能干细胞（hiPSC）生成的剂量依赖性减少。总的来说，我们的数据表明，ST 6 GAL 1在调节hPSC的多能性和分化中起着重要作用，并且可以使用药理学工具来调节人细胞中的多能状态以靶向唾液酸转移酶活性。
Many studies have suggested the significance of glycosyltransferase-mediated macromolecule glycosylation in the regulation of pluripotent states in human pluripotent stem cells (hPSCs). Here, we observed that the sialyltransferase ST6GAL1 was preferentially expressed in undifferentiated hPSCs compared to non-pluripotent cells. A lectin which preferentially recognizes α-2,6 sialylated galactosides showed strong binding reactivity with undifferentiated hPSCs and their glycoproteins, and did so to a much lesser extent with differentiated cells. In addition, downregulation of ST6GAL1 in undifferentiated hPSCs led to a decrease in POU5F1 (also known as OCT4) protein and significantly altered the expression of many genes that orchestrate cell morphogenesis during differentiation. The induction of cellular pluripotency in somatic cells was substantially impeded by the shRNA-mediated suppression of ST6GAL1, partially through interference with the expression of endogenous POU5F1 and SOX2. Targeting ST6GAL1 activity with a sialyltransferase inhibitor during cell reprogramming resulted in a dose-dependent reduction in the generation of human induced pluripotent stem cells (hiPSCs). Collectively, our data indicate that ST6GAL1 plays an important role in the regulation of pluripotency and differentiation in hPSCs, and the pluripotent state in human cells can be modulated using pharmacological tools to target sialyltransferase activity.