Crosstalk between miR-34a and Notch Signaling Promotes Differentiation in Apical Papilla Stem Cells (SCAPs)

J Dent Res. 2014 Jun;93(6):589-95. doi: 10.1177/0022034514531146. Epub 2014 Apr 7.

Abstract

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.

Keywords: cell fate determination; epigenetic; microRNA; stem cells from apical papilla; tooth development; tooth regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adolescent
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Child
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Extracellular Matrix Proteins / genetics
  • Gene Expression Regulation / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Jagged-2 Protein
  • Membrane Proteins / genetics
  • MicroRNAs / physiology*
  • Odontogenesis / genetics
  • Osteocalcin / genetics
  • Osteogenesis / genetics
  • Phosphoproteins / genetics
  • Receptor Cross-Talk / physiology*
  • Receptor, Notch2 / genetics
  • Receptor, Notch3
  • Receptors, Notch / genetics
  • Receptors, Notch / physiology*
  • Repressor Proteins / genetics
  • Sialoglycoproteins / genetics
  • Signal Transduction / physiology*
  • Sp7 Transcription Factor
  • Stem Cells / physiology*
  • Tooth Apex / cytology*
  • Transcription Factor HES-1
  • Transcription Factors / genetics
  • Young Adult

Substances

  • 3' Untranslated Regions
  • Basic Helix-Loop-Helix Transcription Factors
  • Core Binding Factor Alpha 1 Subunit
  • DLL3 protein, human
  • Extracellular Matrix Proteins
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • JAG2 protein, human
  • Jagged-2 Protein
  • MIRN34 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • NOTCH2 protein, human
  • NOTCH3 protein, human
  • Phosphoproteins
  • RUNX2 protein, human
  • Receptor, Notch2
  • Receptor, Notch3
  • Receptors, Notch
  • Repressor Proteins
  • Sialoglycoproteins
  • Sp7 Transcription Factor
  • SP7 protein, human
  • Transcription Factor HES-1
  • Transcription Factors
  • dentin sialophosphoprotein
  • Osteocalcin
  • HES1 protein, human