Chondroitin sulfate is indispensable for pluripotency and differentiation of mouse embryonic stem cells.

Chondroitin sulfate is indispensable for pluripotency and differentiation of mouse embryonic stem cells.
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DOI:
10.1038/srep03701
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发表时间:
2014-01-15
期刊:
影响因子:
4.6
通讯作者:
Kitagawa H
Kitagawa H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Izumikawa T;Sato B;Kitagawa H

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硫酸软骨素(CS)蛋白聚糖存在于几乎所有细胞的表面和细胞外基质中,是早期发育阶段胞质分裂所需的。研究表明,硫酸乙酰肝素(HS)是维持小鼠胚胎干细胞(ESCs)的分化所必需的,而CS的功能尚未阐明。为了阐明CS的作用,我们产生了缺乏CS的葡糖醛酸转移酶-I-敲除ESC。我们发现,CS是必需的,以维持胚胎干细胞的多能性和促进初始ESC承诺分化相比,HS。此外,CS-A和CS-E多糖,而不是CS-C多糖,结合E-钙粘蛋白和增强ESC分化。在软骨素酶ABC消化的野生型ESC中,多谱系分化受到抑制。总的来说,这些结果表明,CS是一种新的决定因素,在控制功能完整性的胚胎干细胞通过结合E-钙粘蛋白。
Chondroitin sulfate (CS) proteoglycans are present on the surfaces of virtually all cells and in the extracellular matrix and are required for cytokinesis at early developmental stages. Studies have shown that heparan sulfate (HS) is essential for maintaining mouse embryonic stem cells (ESCs) that are primed for differentiation, whereas the function of CS has not yet been elucidated. To clarify the role of CS, we generated glucuronyltransferase-I-knockout ESCs lacking CS. We found that CS was required to maintain the pluripotency of ESCs and promoted initial ESC commitment to differentiation compared with HS. In addition, CS-A and CS-E polysaccharides, but not CS-C polysaccharides, bound to E-cadherin and enhanced ESC differentiation. Multiple-lineage differentiation was inhibited in chondroitinase ABC-digested wild-type ESCs. Collectively, these results suggest that CS is a novel determinant in controlling the functional integrity of ESCs via binding to E-cadherin.
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