title: Depletion of histone demethylase KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of stem cells from apical papilla.
abstract: Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. The histone demethylase, lysine (K)-specific demethylase 2A (KDM2A), is evolutionarily conserved and ubiquitously expressed members of the JmjC-domain-containing histone demethylase family. A previous study determined that KDM2A can regulate the cell proliferation and osteo/dentinogenic differentiation of MSCs. It is not known whether KDM2A is involved in the other cell lineages differentiation of MSCs. Here, we show that depletion of KDM2A by short hairpin RNAs can enhance adipogenic and chondrogenic differentiation potentials in human stem cells from apical papilla (SCAPs). We found that the stemness-related genes, SOX2, and the embryonic stem cell master transcription factor, NANOG were significantly increased after silence of KDM2A in SCAPs. Moreover, we found that knock-down of the KDM2A co-factor, BCOR also up-regulated the mRNA levels of SOX2 and NANOG. Furthermore, Chromatin immunoprecipitation assays demonstrate that silence of KDM2A increased the histone H3 Lysine 4 (H3K4) trimethylation in the SOX2 and NANOG locus and regulates its expression. In conclusion, our results suggested that depletion of KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of SCAPs by up-regulated SOX2 and NANOG, BCOR also involved in this regulation as co-factor, and provided useful information to understand the molecular mechanism underlying directed differentiation in MSCs.
authors.affiliation: Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Dong
authors.forename: Rui
authors.initials: R
authors.lastname: Yao
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Songlin
authors.initials: S
authors.lastname: Wang
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Fan
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000293:Adolescent; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000235:genetics*; D003771:Dental Papilla / Q000166:cytology* / Q000201:enzymology; D044783:F-Box Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000037:antagonists & inhibitors* / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology; D008745:Methylation; D008964:Molar, Third / Q000166:cytology; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D044783:F-Box Proteins; D034741:RNA, Small Interfering; D056484:Jumonji Domain-Containing Histone Demethylases; C534524:KDM2A protein, human
keywords: Adipogenic; Chondrogenic; Histone demethylase; KDM2A; Stem cells from apical papilla (SCAPs)