Wang T T, Tio M, Lee W, Beerheide W, Udolph G
Institute of Medical Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
Biochem Biophys Res Commun. 2007 Jun 15;357(4):1021-7. doi: 10.1016/j.bbrc.2007.04.046. Epub 2007 Apr 18.
Mesenchymal stem cells (MSC) are multipotent and give rise to distinctly differentiated cells from all three germ layers. While umbilical cord blood derived mesenchymal-like cells were previously shown to be capable of differentiating into the neural lineage both in vitro and in vivo, the underlying molecular mechanisms and signal transduction pathways remain to be elucidated. In this study, we show that mesenchymal-like cells from umbilical cord blood are capable of neural differentiation and this capability is mediated by the Protein kinase A (PKA) signal transduction pathway. While activation of PKA via experimental cAMP upregulation leads to outgrowth of neurite-like structures as well as expression of neural marker genes, blocking PKA activity completely abolishes all these features. Thus, our results demonstrate that PKA function is sufficient and required for neurite-like outgrowth and regulation of neural specific gene expression in mesenchymal-like stem cells from cord blood.
间充质干细胞（MSC）具有多能性，可分化为来自所有三个胚层的明显不同的细胞。虽然先前已证明脐带血来源的间充质样细胞能够在体外和体内分化为神经谱系，但其潜在的分子机制和信号转导途径仍有待阐明。在本研究中，我们表明脐带血来源的间充质样细胞能够进行神经分化，并且这种能力是由蛋白激酶A（PKA）信号转导途径介导的。通过实验性上调cAMP激活PKA会导致神经突样结构的生长以及神经标志物基因的表达，而阻断PKA活性则会完全消除所有这些特征。因此，我们的结果表明，PKA功能对于脐带血来源的间充质样干细胞中神经突样生长和神经特异性基因表达的调节是充分且必要的。
