title

مهار فارماکولوژیک مسیر پیام رسانی Notch منجر به توقف چرخه سلولی می شود و بیان ژن های ascl1 و neurogenin2 را در نوروسفیر های مشتق از سلول های بنیادی پالپ دندان افزایش می دهد

نیاپور, علی and قاسمی حمیدآبادی, هاتف and نیاپور, نازیلا and محمدی, پرهام سعداله and شریفی پاسندی, مرضیه and ملک زاده, ودود (1398) مهار فارماکولوژیک مسیر پیام رسانی Notch منجر به توقف چرخه سلولی می شود و بیان ژن های ascl1 و neurogenin2 را در نوروسفیر های مشتق از سلول های بنیادی پالپ دندان افزایش می دهد. Biotechnology Letter ــ 41 (6-7). pp. 873-887. شاپا 0141-5492

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Official URL: https://link.springer.com/article/10.1007/s10529-0...


Title

Pharmacological Notch pathway inhibition leads to cell cycle arrest and stimulates ascl1 and neurogenin2 genes expression in dental pulp stem cells-derived neurospheres

English Abstract

Objective: Human dental pulp-derived stem cells (hDPSCs) are becoming an attractive source for cell-based neurorestorative therapies. As such, it is important to understand the molecular mechanisms that regulate the differentiation of hDPSCs toward the neuronal fate. Notch signaling plays key roles in neural stem/progenitor cells (NS/PCs) maintenance and prevention of their differentiation. The aim of this study was to address the effects of Notch signaling inhibition on neurosphere formation of hDPSCs and neuronal differentiation of hDPSCs-neurospheres. Results: hDPSCs were isolated from third molar teeth. The cultivated hDPSCs highly expressed CD90 and CD44 and minimally presented CD34 and CD45 surface markers. The osteo/adipogenic differentiation of hDPSCs was documented. hDPSCs were cultured in neural induction medium and N-[N-(3,5-difluorophenacetyl-L-alanyl)]-Sphenylglycine t-butyl ester (DAPT) was applied to impede Notch signaling during transformation into spheres or on the formed neurospheres. Our results showed that the size and number of neurospheres decreased and the expression profile of nestin, sox1 and pax6 genes reduced provided DAPT. Treatment of the formed neurospheres with DAPT resulted in the cleaved Notch1 reduction, G0/G1 arrest and a decline in L-lactate production. DAPT significantly reduced hes1 and hey1 genes, while ascl1 and neurogenin2 expressions augmented. The number of MAP2 positive cells improved in the DAPT-treated group. Conclusions: Our findings demonstrated the Notch activity in hDPSCs- neurospheres. DAPT treatment positively regulated proneural genes expression and increased neuronal-like differentiation.

Item Type:Article
زبان سند : انگلیسی
نویسنده مسئول :علی نیاپور
نویسنده :هاتف قاسمی حمیدآبادی
نویسنده :نازیلا نیاپور
نویسنده :پرهام سعداله محمدی
نویسنده :مرضیه شریفی پاسندی
نویسنده :ودود ملک زاده
Additional Information:IF: 2.154 (2018) Indexing in: ISI, Pubmed/Medline, Scopus, Index medicus, Google scholar
کلیدواژه ها (انگلیسی):hDPSCs, Notch signaling, Gamma secretase inhibitor, Neurosphere, Differentiation, ascl1, Neurogenin2
Subjects:QV pharmacology
WL Nervous system
Divisions:Faculty of Medicine > Department of Basic Sciences > Department of Anatomy
Faculty of Medicine > Department of Basic Sciences > Department of Pharmacology
ID Code:11896
Deposited By: Dr Ali Niapour
Deposited On:20 Mar 1398 10:37
Last Modified:19 Jan 1399 17:13

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