Small molecule induction of neural‐like cells from bone marrow‐mesenchymal stem cells
Small molecule induction of neural‐like cells from bone marrow‐mesenchymal stem cells
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DOI：
10.1002/jcb.24021
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发表时间：
2012-05
影响因子：
4
通讯作者：
Ye Wang;Wen-feng He;Hetao Bian;Chuan Liu;Shiyong Li
中科院分区：
文献类型：
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作者：
Ye Wang;Wen-feng He;Hetao Bian;Chuan Liu;Shiyong Li
骨髓间充质干细胞(MSCs)已被证明能够分化为神经元样细胞，但控制这一过程的确切机制尚不清楚。我们报道了PI3K/AKT信号通路的小分子抑制剂LY294002与MSCs共同孵育6h和12h后，可以抑制MSCs的增殖并促进其向神经元分化，RT-PCR结果显示α-5-β-1整合素在MSCs神经元样细胞中的表达显著增加。有趣的是，这种方法获得的神经元样细胞比MSCs具有更强的黏附能力，这与α-5-β-1整合素的表达和粘着斑激酶的磷酸化有关。而LiCL或GSK-3β-siRNA可减弱上述作用。结果提示，GSK-3β信号的激活可能参与了间充质干细胞的增殖、分化和黏附。此外，这项研究表明，PI3K/AKT信号的小分子调节器可能是旨在治疗神经退行性疾病的干细胞研究的有价值的工具。J.细胞。生物化学。113：1527-1536,2012。©2011 Wiley期刊，Inc.
Bone marrow‐derived mesenchymal stem cells (MSCs) have been demonstrated to be able to differentiate into neuron‐like cell, but the precise mechanisms controlling this process are unclear. We report here that LY294002, a small molecule inhibitor of PI3K/AKT signal pathway, can inhibit proliferation and promote neuronal differentiation of MSCs after MSCs incubated with LY294002 for 6 and 12 h. RT‐PCR results indicated that mRNA expression of α5β1 integrin significantly increased in neuron‐like cell from MSCs. Interestingly, neuron‐like cells derived by this method adhere much more strongly than MSCs, which was related to the expression of α5β1 integrin and FAK phosphorylation. However, these effects could be attenuated by LiCL or GSK‐3β–siRNA. Our results indicate that activation GSK‐3β signaling may be involved in MSCs proliferation, differentiation, and adhesion. Furthermore, this study demonstrates that small molecule regulators of PI3K/AKT signaling may be valuable tools for stem cell research aimed at treatment of neurodegenerative disease. J. Cell. Biochem. 113: 1527–1536, 2012. © 2011 Wiley Periodicals, Inc.