Document Detail

Notch signaling is involved in neurogenic commitment of human periodontal ligament-derived mesenchymal stem cells.
MedLine Citation:
PMID:  23379739     Owner:  NLM     Status:  MEDLINE    
Notch signaling plays critical roles in stem cells by regulating cell fate determination and differentiation. The aim of this study was to evaluate the participation of Notch signaling in neurogenic commitment of human periodontal ligament-derived mesenchymal stem cells (hPDLSCs) and to examine the ability to control differentiation of these cells using modified surfaces containing affinity immobilized Notch ligands. Neurogenic induction of hPDLSCs was performed via neurosphere formation. Cells were aggregated and form spheres as early 1 day in culture. In addition, the induced cells exhibited increased mRNA and protein expression of neuronal markers that is, β3-tubulin and neurofilament. During neuronal differentiation, a significant increase of Hes1 and Hey1 mRNA expression was noted. Using pharmacological inhibition (γ-secretase inhibitor) or genetic manipulation (overexpression of dominant negative mastermind-like transcription co-activators), neurosphere formation was attenuated and a marked decrease in neurogenic mRNA expression was observed. To confirm the role of Notch signaling in neuronal differentiation of hPDLSCs, the Notch ligand, Jagged-1, is bound to the surface using an affinity immobilization technique. The hPDLSC cultured on a Jagged-1-modified surface had increased expression of Notch signaling target genes, Hes-1 and Hey-1, confirming the activity and potency of surface-bound Jagged-1. Further, hPDLSC on surface-bound Jagged-1 under serum-free conditions showed multiple long and thin neurite-like extensions, and an increase in the expression of neurogenic mRNA markers was observed. Pretreatment of the cells with γ-secretase inhibitor, DAPT, before seeding on the Jagged-1-modified surface blocked development of the neurite-like morphology. Together, the results in this study suggest the involvement of Notch signaling in neurogenic commitment of hPDLSCs.
Thanaphum Osathanon; Jeeranan Manokawinchoke; Nunthawan Nowwarote; Panuroot Aguilar; Tanapat Palaga; Prasit Pavasant
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-02-12
Journal Detail:
Title:  Stem cells and development     Volume:  22     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-11     Completed Date:  2013-10-31     Revised Date:  2014-04-15    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1220-31     Citation Subset:  IM    
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MeSH Terms
Amyloid Precursor Protein Secretases / antagonists & inhibitors
Basic Helix-Loop-Helix Transcription Factors / genetics
Calcium-Binding Proteins / genetics,  metabolism
Cell Cycle Proteins / genetics
Cell Differentiation / drug effects,  genetics
Cells, Cultured
Dipeptides / pharmacology
Gene Expression / drug effects
HEK293 Cells
Homeodomain Proteins / genetics
Intercellular Signaling Peptides and Proteins / genetics,  metabolism
Membrane Proteins / genetics,  metabolism
Mesenchymal Stromal Cells / cytology,  metabolism*
Microscopy, Fluorescence
Neurons / cytology,  metabolism*
Periodontal Ligament / cytology
Receptors, Notch / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects,  genetics*
Tubulin / genetics,  metabolism
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Calcium-Binding Proteins; 0/Cell Cycle Proteins; 0/Dipeptides; 0/HEY1 protein, human; 0/Homeodomain Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; 0/Receptors, Notch; 0/Tubulin; 0/beta III-tubulin protein, human; 134324-36-0/Serrate proteins; 149348-15-2/HES1 protein, human; EC 3.4.-/Amyloid Precursor Protein Secretases

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