title: Protein Interacting with Never in Mitosis A-1 Induces Glutamatergic and GABAergic Neuronal Differentiation in Human Dental Pulp Stem Cells.
abstract: BACKGROUND
  The purpose of this study was to investigate the role of protein interacting with never in mitosis A-1 (PIN1) in the neuronal or glial differentiation of human dental pulp stem cells (hDPSCs) and whether PIN1 can regulate determination of neuronal sub-phenotype.
  
  
  METHODS
  After magnetic-activated cell sorting to separate CD34(+)/c-kit(+)/STRO-1(+) hDPSCs, cells were cultured in neurogenic medium. Differentiation was measured as Nissl staining and marker protein or mRNA expression by reverse transcriptase polymerase chain reaction, immunofluorescence, and flow cytometric analysis.
  
  
  RESULTS
  PIN1 mRNA levels were upregulated in a time-dependent fashion during neurogenic differentiation. The PIN1 inhibitor juglone suppressed neuronal differentiation but promoted glial differentiation as assessed by the number of Nissl-positive cells and mRNA expression of neuronal markers (nestin, βIII-tubulin, and NeuN) and a glial marker (glial fibrillary acidic protein). Conversely, overexpression of PIN1 by infection with adenovirus-PIN1 increased neuronal differentiation but decreased glial differentiation. Moreover, PIN1 overexpression increased the percentage of glutamatergic and GABAergic cells but decreased that of dopaminergic cells among total NeuN-positive hDPSCs.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that PIN1 overexpression induced glutamatergic and GABAergic neuronal differentiation but suppressed glial differentiation of hDPSCs, suggesting that enhancing PIN expression is important to obtain human glutamatergic and GABAergic neurons from hDPSCs.
authors.affiliation: Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Tissue Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Young-Ah
authors.initials: YA
authors.lastname: Cho
authors.affiliation: Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Duck-Su
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Tissue Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Miyeoun
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Tissue Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Won-Jung
authors.initials: WJ
authors.lastname: Bae
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Soojung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Tissue Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea. Electronic address: eckim@khu.ac.kr.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D015415:Biomarkers; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D012333:RNA, Messenger; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: Glial cells; PIN1; human dental pulp stem cells; neural differentiation; neuron