|Notch signaling is involved in neurogenic commitment of human periodontal ligament-derived mesenchymal stem cells.|
|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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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2013-02-12|
|Title: Stem cells and development Volume: 22 ISSN: 1557-8534 ISO Abbreviation: Stem Cells Dev. Publication Date: 2013 Apr|
|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|
|Languages: eng Pagination: 1220-31 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
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
Dipeptides / pharmacology
Gene Expression / drug effects
Homeodomain Proteins / genetics
Intercellular Signaling Peptides and Proteins / genetics, metabolism
Membrane Proteins / genetics, metabolism
Mesenchymal Stromal Cells / cytology, metabolism*
Neurons / cytology, metabolism*
Periodontal Ligament / cytology
Receptors, Notch / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects, genetics*
Tubulin / genetics, metabolism
|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|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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