There is more to a lipid than just being a fat: sphingolipid-guided differentiation of oligodendroglial lineage from embryonic stem cells.
There is more to a lipid than just being a fat: sphingolipid-guided differentiation of oligodendroglial lineage from embryonic stem cells.
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DOI：
10.1007/s11064-010-0338-5
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发表时间：
2011-09
影响因子：
4.4
通讯作者：
Bieberich, Erhard
中科院分区：
文献类型：
--
作者：
Bieberich, Erhard
关键词：
Robert K.博士Yu的研究首次表明，鞘糖脂的组成在胚胎发育过程中受到严格调控。我们小组的研究表明，鞘糖脂前体神经酰胺对干细胞分化和凋亡也至关重要。我们的新研究表明，神经酰胺及其衍生物，鞘氨醇-1-磷酸（S1 P），协同作用于胚胎干细胞（ES）分化。当使用来源于ES细胞的神经前体细胞（NPC）进行移植时，残留的多能干细胞（rPS）在干细胞移植后构成肿瘤形成的显著风险。我们在这里表明，rPS细胞不表达S1 P受体S1 P1，这使得它们容易受到神经酰胺或神经酰胺类似物（N-油酰丝氨醇或S18）诱导的细胞凋亡。相反，ES细胞来源的NPC表达S1 P1，并且在S1 P或其前药类似物FTY 720的存在下受到保护。与先前的研究一致，FTY 720处理的NPC主要向少突胶质细胞谱系分化，如通过少突胶质细胞前体细胞（OPC）标志物Olig 2和O 4的表达所测试的。结果，向分化中的ES细胞联合施用S18和FTY 720消除了rPS细胞并促进了少突胶质细胞分化。此外，我们表明，这种组合促进分化的ES细胞来源的NPC向少突胶质细胞系在体内移植到小鼠脑后。
Dr. Robert K. Yu's research showed for the first time that the composition of glycosphingolipids is tightly regulated during embryo development. Studies in our group showed that the glycosphingolipid precursor ceramide is also critical for stem cell differentiation and apoptosis. Our new studies suggest that ceramide and its derivative, sphingosine-1-phosphate (S1P), act synergistically on embryonic stem (ES) cell differentiation. When using neural precursor cells (NPCs) derived from ES cells for transplantation, residual pluripotent stem (rPS) cells pose a significant risk of tumor formation after stem cell transplantation. We show here that rPS cells did not express the S1P receptor S1P1, which left them vulnerable to ceramide or ceramide analog (N-oleoyl serinol or S18)-induced apoptosis. In contrast, ES cell-derived NPCs expressed S1P1 and were protected in the presence of S1P or its pro-drug analog FTY720. Consistent with previous studies, FTY720-treated NPCs differentiated predominantly toward oligodendroglial lineage as tested by the expression of the oligodendrocyte precursor cell (OPC) markers Olig2 and O4. As the consequence, a combined administration of S18 and FTY720 to differentiating ES cells eliminated rPS cells and promoted oligodendroglial differentiation. In addition, we show that this combination promoted differentiation of ES cell-derived NPCs toward oligodendroglial lineage in vivo after transplantation into mouse brain.
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影响因子：
4.8
作者：
Bieberich, E;Kawaguchi, T;Yu, RK
通讯作者：
Yu, RK
影响因子：
4.2
作者：
Duncan, ID
通讯作者：
Duncan, ID
影响因子：
2.9
作者：
Dasgupta, S;Everhart, MB;Hogan, EL
通讯作者：
Hogan, EL
影响因子：
6.5
作者：
Bartke, Nana;Hannun, Yusuf A.
通讯作者：
Hannun, Yusuf A.
DOI：
10.1124/jpet.107.123927
发表时间：
2007-11-01
影响因子：
3.5
作者：
Coelho, Rochelle P.;Payne, Shawn G.;Sato-Bigbee, Carmen
通讯作者：
Sato-Bigbee, Carmen