Cobalt chloride induces neuronal differentiation of human mesenchymal stem cells through upregulation of microRNA-124a.
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.
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, South Korea; Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 135-710, South Korea.
Eun Su
ES
Jeon
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, South Korea; Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 135-710, South Korea.
Jin Hee
JH
Shin
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, South Korea.
Su Jin
SJ
Hwang
Medical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
Gyeong Joon
GJ
Moon
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, South Korea; Department of Neurology, Samsung Medical Center, Sungkyunkwan University, Seoul 135-710, South Korea.
Oh Young
OY
Bang
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, South Korea; Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 135-710, South Korea. Electronic address: hyeonhkim@skku.edu.
Hyeon Ho
HH
Kim
D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology; D055758:SOX9 Transcription Factor / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D003035:Cobalt; C018021:cobaltous chloride
Cobalt chloride; Human mesenchymal stem cells; Hypoxia-inducible factor-1α; MicroRNA-124a; Neuronal differentiation