Forskolin and IBMX Induce Neural Transdifferentiation of MSCs Through Downregulation of the NRSF
Forskolin and IBMX Induce Neural Transdifferentiation of MSCs Through Downregulation of the NRSF
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DOI：
10.1038/s41598-019-39544-0
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发表时间：
2019-02
影响因子：
4.6
通讯作者：
Ryan Thompson;C. Casali;C. Chan
中科院分区：
文献类型：
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作者：
Ryan Thompson;C. Casali;C. Chan
间充质干细胞的神经分化是一个有争议的现象，因为它需要跨越中胚层和外胚层屏障进行转分化。然而，一些实验室已经观察到MSCs能够被诱导表达神经特征。之前，我们证明了camp升高剂，福斯克林和IBMX，诱导MSCs的神经样分化，包括神经标记物的表达和对神经递质的敏感性增加。然而，由于forskolin和IBMX可以通过细胞内第二信使cAMP引起广泛的影响，因此需要更好的机制理解。在这里，我们发现forskolin和IBMX的神经诱导依赖于主转录调控因子神经元限制性沉默因子（NRSF）及其下游靶基因的表达下调。由于已知NRSF的沉默可启动神经分化，这表明forskolin和IBMX可导致间充质干细胞转分化为神经谱系。
Neural differentiation of mesenchymal stem cells is a controversial phenomenon, as it would require transdifferentiation across the mesoderm-ectoderm barrier. However, several laboratories have observed that MSCs are able to be induced to express neural characteristics. Previously, we demonstrated that the cAMP-elevating agents, forskolin and IBMX, induced neural-like differentiation of MSCs, including expression of neural markers and increased sensitivity to neurotransmitters. However, due to the broad range of effects that forskolin and IBMX can elicit through the intracellular second messenger, cAMP, a better mechanistic understanding is required. Here, we show that neural induction by forskolin and IBMX is dependent on downregulation of expression of the master transcriptional regulator, neuron restrictive silencer factor (NRSF), and its downstream target genes. Since silencing of NRSF is known to initiate neural differentiation, it suggests that forskolin and IBMX result in transdifferentiation of MSCs into a neural lineage.