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Cobalt chloride induces neuronal differentiation of human mesenchymal stem cells through upregulation of microRNA-124a
Authors:Eun Su Jeon  Jin Hee Shin  Su Jin Hwang  Gyeong Joon Moon  Oh Young Bang  Hyeon Ho Kim
Institution:1. Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, South Korea;2. Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 135-710, South Korea;3. Department of Neurology, Samsung Medical Center, Sungkyunkwan University, Seoul 135-710, South Korea;4. Medical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea
Abstract:Human mesenchymal stem cells (hMSCs) are known to have the capacity to differentiate into various cell types, including neurons. To examine our hypothesis that miRNA was involved in neuronal differentiation of hMSCs, CoCl2, a hypoxia-mimicking agent was used to induce neuronal differentiation, which was assessed by determining the expression of neuronal markers such as nestin and Tuj1. Treatment of hMSCs with CoCl2 led to increased expression of miR-124a, a neuron-specific miRNA. HIF-1α silencing and JNK inhibition abolished CoCl2-induced miR-124a expression, suggesting that JNK and HIF-1α signals were required for the miR-124a expression induced by CoCl2 in hMSCs. Overexpression of miR-124a or CoCl2 treatment suppressed the expression of anti-neural proteins such as SCP1 and SOX9. Silencing of both SCP1 and SOX9 induced neuronal differentiation of hMSCs, indicating that suppression of miR-124a targets is important for CoCl2-induced neuronal differentiation of hMSCs. Knockdown of HIF-1α or inhibition of JNK restored the expression of SCP1 and SOX9 in CoCl2-treated cells. Inhibition of miR-124a blocked CoCl2-induced suppression of SCP1 and SOX9 and abolished CoCl2-induced neuronal differentiation of hMSCs. Taken together, we demonstrate that miR-124a is critically regulates CoCl2-induced neuronal differentiation of hMSCs by suppressing the expression of SCP1 and SOX9.
Keywords:Human mesenchymal stem cells  Neuronal differentiation  Cobalt chloride  Hypoxia-inducible factor-1α  MicroRNA-124a
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