Notch/Wnt Cross-Signalling Regulates Stemness Of Dental Pulp Stem Cells Through Expression Of Neural Crest And Core Pluripotency Factors

Dental pulp stem cells (DPSCs) from adult teeth express neural crest (NC) markers together with core transcriptional factors associated with stem cell pluripotency, such as Oct4a, Sox2, c-Myc, Rex1, Stella/Dppa3, Ssea1/Fut4, Lin28 and Nanog. The possibility to boost the natural stemness features of...

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Autores: Uribe-Echevarria Zubizarreta, Verónica, Luzuriaga González, Jon, García Gallastegui, Patricia, Agliano, Alice, Unda Rodríguez, Fernando José, Ibarretxe Bilbao, Gaskon
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/27568
Acceso en línea:http://hdl.handle.net/10810/27568
Access Level:acceso abierto
Palabra clave:dental pulp stem cells
multipotency
self-renewal
pluripotency core factors
neural crest
stemness and differentiation
osteogenesis
adipogenesis
Notch
Wnt
BIO
DAPT
Wnt-3a
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spelling Notch/Wnt Cross-Signalling Regulates Stemness Of Dental Pulp Stem Cells Through Expression Of Neural Crest And Core Pluripotency FactorsUribe-Echevarria Zubizarreta, VerónicaLuzuriaga González, JonGarcía Gallastegui, PatriciaAgliano, AliceUnda Rodríguez, Fernando JoséIbarretxe Bilbao, Gaskondental pulp stem cellsmultipotencyself-renewalpluripotency core factorsneural creststemness and differentiationosteogenesisosteogenesisadipogenesisNotchWntBIODAPTWnt-3aDental pulp stem cells (DPSCs) from adult teeth express neural crest (NC) markers together with core transcriptional factors associated with stem cell pluripotency, such as Oct4a, Sox2, c-Myc, Rex1, Stella/Dppa3, Ssea1/Fut4, Lin28 and Nanog. The possibility to boost the natural stemness features of DPSCs by mild methods, that do not involve gene and/or chromatin modification or gene transfection, is highly desirable for cell therapy. Canonical Wnt and Notch are two highly conserved developmental signalling pathways that are involved in NC emergence and stem cell self-renewal. We determined that both pathways coordinate to regulate the expression of core pluripotency and NC factors in DPSCs. Pharmacological inhibition of the Notch pathway for 48 h, by the gamma-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), abolished the expression of NC and core factors. In addition, it induced a silencing of the canonical Wnt signalling and a clear reduction in the stemness potential of DPSCs, as shown by a reduced ability to generate mature, fully differentiated osteoblasts and adipocytes. Conversely, pharmacological activation of the Wnt pathway for 48 h, by either the glycogen synthase kinase 3 beta (GSK3-beta) inhibitor 6-bromoindirubin-3'-oxime (BIO) or the human recombinant protein Wnt-3a, not only largely increased the expression of NC and core factors, but also increased the efficiency of DPSCs to differentiate into mature osteoblasts and adipocytes. These results showed that a short preconditioning activation of Wnt/Notch signalling by small molecules and/or recombinant proteins enhanced the stemness and potency of DPSCs in culture, which could be useful for optimising the therapeutic use of these and other tissue-specific stem cells.Technical and human support provided by the analytical microscopy service of SGIKER (UPV/EHU, MINECO, GV/EJ, ERDF and ESF) is gratefully acknowledged. This work was funded by the UPV/EHU (GIU16/66, UFI 11/44) and the Basque Government (GV/EJ; IT831-13). V.U. received a fellowship from The Global Training Grant (GV/EJ) to fund a research stage at The Institute of Cancer Research (London, UK).AO Research Institute Davos-Ari201820182017info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/27568reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.ecmjournal.org/papers/vol034/vol034a16.phpinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-sa/3.0/es/Reconocimiento-CompartirIgual CC BY-SA Esta licencia permite a otros re-mezclar, modificar y desarrollar sobre tu obra incluso para propósitos comerciales, siempre que te atribuyan el crédito y licencien sus nuevas obras bajo idénticos términos. Esta licencia es a menuda comparada con las licencias de "copyleft" y las de software "open source". Cualquier obra nueva basada en la tuya , lo será bajo la misma licencia, de modo que cualquier obra derivada permitirá también su uso comercial. Esta licencia es la utilizada por Wikipedia y se recomienda para aquellos materiales que puedan beneficiarse de la incorporación de contenido proveniente de Wiikipedia u otros proyectos licenciados de la misma forma.Atribución-CompartirIgual 3.0 Españaoai:addi.ehu.eus:10810/275682026-06-18T09:23:17Z
dc.title.none.fl_str_mv Notch/Wnt Cross-Signalling Regulates Stemness Of Dental Pulp Stem Cells Through Expression Of Neural Crest And Core Pluripotency Factors
title Notch/Wnt Cross-Signalling Regulates Stemness Of Dental Pulp Stem Cells Through Expression Of Neural Crest And Core Pluripotency Factors
spellingShingle Notch/Wnt Cross-Signalling Regulates Stemness Of Dental Pulp Stem Cells Through Expression Of Neural Crest And Core Pluripotency Factors
Uribe-Echevarria Zubizarreta, Verónica
dental pulp stem cells
multipotency
self-renewal
pluripotency core factors
neural crest
stemness and differentiation
osteogenesis
osteogenesis
adipogenesis
Notch
Wnt
BIO
DAPT
Wnt-3a
title_short Notch/Wnt Cross-Signalling Regulates Stemness Of Dental Pulp Stem Cells Through Expression Of Neural Crest And Core Pluripotency Factors
title_full Notch/Wnt Cross-Signalling Regulates Stemness Of Dental Pulp Stem Cells Through Expression Of Neural Crest And Core Pluripotency Factors
title_fullStr Notch/Wnt Cross-Signalling Regulates Stemness Of Dental Pulp Stem Cells Through Expression Of Neural Crest And Core Pluripotency Factors
title_full_unstemmed Notch/Wnt Cross-Signalling Regulates Stemness Of Dental Pulp Stem Cells Through Expression Of Neural Crest And Core Pluripotency Factors
title_sort Notch/Wnt Cross-Signalling Regulates Stemness Of Dental Pulp Stem Cells Through Expression Of Neural Crest And Core Pluripotency Factors
dc.creator.none.fl_str_mv Uribe-Echevarria Zubizarreta, Verónica
Luzuriaga González, Jon
García Gallastegui, Patricia
Agliano, Alice
Unda Rodríguez, Fernando José
Ibarretxe Bilbao, Gaskon
author Uribe-Echevarria Zubizarreta, Verónica
author_facet Uribe-Echevarria Zubizarreta, Verónica
Luzuriaga González, Jon
García Gallastegui, Patricia
Agliano, Alice
Unda Rodríguez, Fernando José
Ibarretxe Bilbao, Gaskon
author_role author
author2 Luzuriaga González, Jon
García Gallastegui, Patricia
Agliano, Alice
Unda Rodríguez, Fernando José
Ibarretxe Bilbao, Gaskon
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv dental pulp stem cells
multipotency
self-renewal
pluripotency core factors
neural crest
stemness and differentiation
osteogenesis
osteogenesis
adipogenesis
Notch
Wnt
BIO
DAPT
Wnt-3a
topic dental pulp stem cells
multipotency
self-renewal
pluripotency core factors
neural crest
stemness and differentiation
osteogenesis
osteogenesis
adipogenesis
Notch
Wnt
BIO
DAPT
Wnt-3a
description Dental pulp stem cells (DPSCs) from adult teeth express neural crest (NC) markers together with core transcriptional factors associated with stem cell pluripotency, such as Oct4a, Sox2, c-Myc, Rex1, Stella/Dppa3, Ssea1/Fut4, Lin28 and Nanog. The possibility to boost the natural stemness features of DPSCs by mild methods, that do not involve gene and/or chromatin modification or gene transfection, is highly desirable for cell therapy. Canonical Wnt and Notch are two highly conserved developmental signalling pathways that are involved in NC emergence and stem cell self-renewal. We determined that both pathways coordinate to regulate the expression of core pluripotency and NC factors in DPSCs. Pharmacological inhibition of the Notch pathway for 48 h, by the gamma-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), abolished the expression of NC and core factors. In addition, it induced a silencing of the canonical Wnt signalling and a clear reduction in the stemness potential of DPSCs, as shown by a reduced ability to generate mature, fully differentiated osteoblasts and adipocytes. Conversely, pharmacological activation of the Wnt pathway for 48 h, by either the glycogen synthase kinase 3 beta (GSK3-beta) inhibitor 6-bromoindirubin-3'-oxime (BIO) or the human recombinant protein Wnt-3a, not only largely increased the expression of NC and core factors, but also increased the efficiency of DPSCs to differentiate into mature osteoblasts and adipocytes. These results showed that a short preconditioning activation of Wnt/Notch signalling by small molecules and/or recombinant proteins enhanced the stemness and potency of DPSCs in culture, which could be useful for optimising the therapeutic use of these and other tissue-specific stem cells.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/27568
url http://hdl.handle.net/10810/27568
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.ecmjournal.org/papers/vol034/vol034a16.php
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-sa/3.0/es/
Atribución-CompartirIgual 3.0 España
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-sa/3.0/es/
Atribución-CompartirIgual 3.0 España
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv AO Research Institute Davos-Ari
publisher.none.fl_str_mv AO Research Institute Davos-Ari
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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