Crosstalk between miR-34a and Notch Signaling Promotes Differentiation in Apical Papilla Stem Cells (SCAPs).
Stem cells from the apical papilla (SCAPs) are important for the formation and regeneration of root dentin. Here, we examined the expression of Notch signaling components in SCAPs and investigated crosstalk between microRNA miR-34aand Notch signaling during cell differentiation. We found that human SCAPs express NOTCH2, NOTCH3, JAG2, DLL3, and HES1, and we tested the relationship between Notch signaling and both cell differentiation and miR-34a expression. NOTCH activation in SCAPs inhibited cell differentiation and up-regulated the expression of miR-34a, whereas miR-34a inhibited Notch signaling in SCAPs by directly targeting the 3'UTR of NOTCH2 and HES1 mRNA and suppressing the expression of NOTCH2, N2ICD, and HES1. DSPP, RUNX2, OSX, and OCN expression was consequently up-regulated. Thus, Notch signaling in human SCAPs plays a vital role in maintenance of these cells. miR-34a interacts with Notch signaling and promotes both odontogenic and osteogenic differentiation of SCAPs.
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041 West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041.
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Sun
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041 West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041 Program in Craniofacial and Mesenchymal Biology and Departments of Orofacial Sciences and Pediatrics, University of California, San Francisco, CA 94143, USA.
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M
Wan
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041.
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Xu
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041.
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B
Gao
West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041.
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Y
Zhou
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041 West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041.
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J
Sun
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041 West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041.
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Cheng
Program in Craniofacial and Mesenchymal Biology and Departments of Orofacial Sciences and Pediatrics, University of California, San Francisco, CA 94143, USA.
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Klein
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041 West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041.
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X
Zhou
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041 West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China, 610041 zhenglw399@hotmail.com.
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Zheng
D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000072101:Jagged-2 Protein; D008565:Membrane Proteins / Q000235:genetics; D035683:MicroRNAs / Q000502:physiology*; D009805:Odontogenesis / Q000235:genetics; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D020239:Receptor Cross-Talk / Q000502:physiology*; D051883:Receptor, Notch2 / Q000235:genetics; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D000076182:Sp7 Transcription Factor; D013234:Stem Cells / Q000502:physiology*; D019227:Tooth Apex / Q000166:cytology*; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult; D000099311:Dentin Sialophosphoprotein
D020413:3' Untranslated Regions; D051792:Basic Helix-Loop-Helix Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; D035683:MicroRNAs; D015675:Osteocalcin; D010750:Phosphoproteins; D051883:Receptor, Notch2; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D012097:Repressor Proteins; D012795:Sialoglycoproteins; D000076182:Sp7 Transcription Factor; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; D000099311:Dentin Sialophosphoprotein; C496666:DLL3 protein, human; C490504:JAG2 protein, human; C522425:MIRN34 microRNA, human; C497764:NOTCH2 protein, human; C499374:NOTCH3 protein, human; C493709:RUNX2 protein, human; C478163:SP7 protein, human; C078493:HES1 protein, human
cell fate determination; epigenetic; microRNA; stem cells from apical papilla; tooth development; tooth regeneration