title: Cellular Prion Protein Promotes Neuronal Differentiation of Adipose-Derived Stem Cells by Upregulating miRNA-124.
abstract: The cellular prion protein (PrP(C)) is a highly conserved glycoprotein anchored by glycosylphosphatidylinositol (GPI) to the cell surface and is also the source of pathogenic agent of scrapie prion protein (PrP(Sc)). Numerous researches have suggested putative physiological roles for PrP(C), including protection from ischemic and excitotoxic lesions, and participation in cell signaling and differentiation. Here, we demonstrated that PrP(C) positively regulates neuronal differentiation of mouse adipose-derived stem cells (ADSCs). The small C-terminal domain phosphatase 1 (SCP1) expression was knocked down by gene silencing. The mRNA expression of miRNA-124 and PrP(C) was measured with quantitative PCR. Western blot analysis was used to detect the protein levels of nestin, βIII-tubulin, and SCP1, and dual-luciferase reporter assay was performed to test the target of miRNA-124. The expression level of PrP(C) was found to increase steadily during neuron-like differentiation process, and PrP(C) knockout resulted in the reduction of neuron-like cell markers. We further showed that miRNA-124 could directly target SCP1-3'-untranslated region to decrease small C-terminal domain phosphatase 1 (SCP1) SCP1, and that miRNA-124 expression is regulated by PrP(C). Our results suggest that PrP(C) may play a key role in the neuronal differentiation of ADSC through modulating miRNA-124-SCP1 axis. To date, this is the first time strong evidence for the involvement of PrP(C) in the neuronal differentiation of ADSC is reported.
authors.affiliation: Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Fushan
authors.initials: F
authors.lastname: Shi
authors.affiliation: College of Animal Sciences and Technology, Zhejiang A&F University, Lin'an, 311300, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Tiancheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Trustchem Co., Ltd., Nanjing, 210029, China.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kouadir
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China. songhua@zju.edu.cn.
authors.forename: Songhua
authors.initials: S
authors.lastname: Hu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D000072002:Prion Proteins / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D064231:Nestin; D000072002:Prion Proteins; D014404:Tubulin; D010749:Phosphoprotein Phosphatases; C000608368:Scp1 protein, mouse
keywords: ADSC; Neuronal differentiation; PrPC