Lee Yi-Jang, Hung Shih-Chieh, Chu Mien-Sheng
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
Stem Cells Cloning. 2010 Nov 23;3:165-73. doi: 10.2147/SCCAA.S14388. eCollection 2010.
The use of in vitro oligodendrocyte differentiation for transplantation of stem cells to treat demyelinating diseases is an important consideration. In this study, we investigated the effects of serum on glia and oligodendrocyte differentiation from human mesenchymal stem cells (KP-hMSCs). We found that serum deprivation resulted in a reversible downregulation of glial- and oligodendrocyte-specific markers. Serum stimulated expression of oligodendrocyte markers, such as galactocerebroside, as well as Notch1 and JAK1 transcripts. Inhibition of Notch1 activation by the Notch inhibitor, MG132, led to enhanced expression of a serum-stimulated oligodendrocyte marker. This marker was undetectable in serum-deprived KP-hMSCs treated with MG132, suggesting that inhibition of Notch1 function is additive to serum-stimulated oligodendrocyte differentiation. Furthermore, a dominant-negative mutant RBP-J protein also inhibited Notch1 function and led to upregulation of oligodendrocyte-specific markers. Our results demonstrate that serum-stimulated oligodendrocyte differentiation is enhanced by the inhibition of Notch1-associated functions.
利用体外少突胶质细胞分化进行干细胞移植以治疗脱髓鞘疾病是一个重要的研究方向。在本研究中，我们调查了血清对人骨髓间充质干细胞（KP-hMSCs）向神经胶质细胞和少突胶质细胞分化的影响。我们发现血清剥夺导致神经胶质细胞和少突胶质细胞特异性标志物的表达可逆性下调。血清刺激少突胶质细胞标志物的表达，如半乳糖脑苷脂，以及Notch1和JAK1转录本。Notch抑制剂MG132抑制Notch1激活导致血清刺激的少突胶质细胞标志物表达增强。在用MG132处理的血清剥夺的KP-hMSCs中未检测到该标志物，这表明抑制Notch1功能对血清刺激的少突胶质细胞分化具有累加作用。此外，显性负性突变体RBP-J蛋白也抑制Notch1功能并导致少突胶质细胞特异性标志物上调。我们的结果表明，抑制Notch1相关功能可增强血清刺激的少突胶质细胞分化。
