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Publication : Heparan sulfate regulates self-renewal and pluripotency of embryonic stem cells.

First Author  Sasaki N Year  2008
Journal  J Biol Chem Volume  283
Issue  6 Pages  3594-606
PubMed ID  18024963 Mgi Jnum  J:131597
Mgi Id  MGI:3774047 Doi  10.1074/jbc.M705621200
Citation  Sasaki N, et al. (2008) Heparan sulfate regulates self-renewal and pluripotency of embryonic stem cells. J Biol Chem 283(6):3594-606
abstractText  Embryonic stem (ES) cell self-renewal and pluripotency are maintained by several signaling cascades and by expression of intrinsic factors, such as Oct3/4 and Nanog. The signaling cascades are activated by extrinsic factors, such as leukemia inhibitory factor, bone morphogenic protein, and Wnt. However, the mechanism that regulates extrinsic signaling in ES cells is unknown. Heparan sulfate (HS) chains are ubiquitously present as the cell surface proteoglycans and are known to play crucial roles in regulating several signaling pathways. Here we investigated whether HS chains on ES cells are involved in regulating signaling pathways that are important for the maintenance of ES cells. RNA interference-mediated knockdown of HS chain elongation inhibited mouse ES cell self-renewal and induced spontaneous differentiation of the cells into extraembryonic endoderm. Furthermore, autocrine/paracrine Wnt/beta-catenin signaling through HS chains was found to be required for the regulation of Nanog expression. We propose that HS chains are important for the extrinsic signaling required for mouse ES cell self-renewal and pluripotency.
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