title: Inhibition of GSK-3β enhances neural differentiation in unrestricted somatic stem cells.
abstract: GSK-3β is a key molecule in several signalling pathways, including the Wnt/β-catenin signalling pathway. There is increasing evidence suggesting Wnt/β-catenin signalling is involved in the neural differentiation of embryonic, somatic and neural stem cells. However, a large body of evidence indicates that this pathway maintains stem cells in a proliferative state. To address this controversy, we have investigated whether the Wnt/β-catenin pathway is present and involved in the neural differentiation of newly introduced USSCs (unrestricted somatic stem cells). Our results indicate that the components of Wnt/β-catenin signalling are present in undifferentiated USSCs. We also show that the treatment of neurally induced USSCs with BIO (6-bromoindirubin-3'-oxime), a specific GSK-3β inhibitor and Wnt activator, for 5 and 10 days results in increased expression of a general neuronal marker (β-tubulin III). Moreover, the expression of pGSK-3β and stabilized β-catenin increased by BIO in neurally induced USSCs, indicates that the Wnt pathway is activated and functional in these cells. Thus, inhibition of GSK-3β in USSCs enhances their neural differentiation, which suggests a positive role of the Wnt/β-catenin signalling pathway towards neural fate.
authors: Developmental Biology Laboratory, School of Biology, College of Science, University of Tehran, Tehran 141556455, Iran.
authors: Fatemeh Vahid
authors: FV
authors: Dastjerdi
authors: Bahman
authors: B
authors: Zeynali
authors: Azita Parvaneh
authors: AP
authors: Tafreshi
authors: Anahita
authors: A
authors: Shahraz
authors: Mahin Sadat
authors: MS
authors: Chavoshi
authors: Irandokht Khaki
authors: IK
authors: Najafabadi
authors: Marzieh Mowlavi
authors: MM
authors: Vardanjani
authors: Amir
authors: A
authors: Atashi
authors: Masoud
authors: M
authors: Soleimani
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D021581:Active Transport, Cell Nucleus; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D055495:Neurogenesis; D010091:Oximes / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C483321:6-bromoindirubin-3'-oxime; C495270:CTNNB1 protein, human; D007211:Indoles; D010091:Oximes; C498585:TUBB3 protein, human; D014404:Tubulin; D051176:beta Catenin; D014212:Tretinoin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D015056:1-Methyl-3-isobutylxanthine