Dermatan sulphate promotes neuronal differentiation in mouse and human stem cells.


Ogura C(1), Hirano K(2), Mizumoto S(3), Yamada S(3), Nishihara S(1)(4).
Author information:
(1)Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan.
(2)Molecular Neurophysiology Research Group, Biomedical Research Institute, The National Institute of Advanced Industrial Science and Technology
(AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
(3)Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Aichi 468-8503, Japan.
(4)Glycan & Life System Integration Center
(GaLSIC), Faculty of Science and Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan.


Dermatan sulphate (DS), a glycosaminoglycan, is present in the extracellular matrix and on the cell surface. Previously, we showed that heparan sulphate plays a key role in the maintenance of the undifferentiated state in mouse embryonic stem cells (mESCs) and in the regulation of their differentiation. Chondroitin sulphate has also been to be important for pluripotency and differentiation of mESCs. Keratan sulphate is a marker of human pluripotent stem cells. To date, however, the function of DS in mESCs has not been clarified. Dermatan 4 sulfotransferase 1, which transfers sulphate to the C-4 hydroxyl group of N-acetylgalactosamine of DS, contributes to neuronal differentiation of mouse neural progenitor cells. Therefore, we anticipated that neuronal differentiation would be induced in mESCs in culture by the addition of DS. To test this expectation, we investigated neuronal differentiation in mESCs and human neural stem cells (hNSCs) cultures containing DS. In mESCs, DS promoted neuronal differentiation by activation of extracellular signal-regulated kinase 1/2 and also accelerated neurite outgrowth. In hNSCs, DS promoted neuronal differentiation and neuronal migration, but not neurite outgrowth. Thus, DS promotes neuronal differentiation in both mouse and human stem cells, suggesting that it offers a novel method for efficiently inducing neuronal differentiation.