Modulation of mouse embryonic stem cell proliferation and neural differentiation by the P2X7 receptor.

<h4>Background</h4>Novel developmental functions have been attributed to the P2X7 receptor (P2X7R) including proliferation stimulation and neural differentiation. Mouse embryonic stem cells (ESC), induced with retinoic acid to neural differentiation, closely assemble processes occurring...

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Autores principales: Talita Glaser, Sophia La Banca de Oliveira, Arquimedes Cheffer, Renata Beco, Patrícia Martins, Maynara Fornazari, Claudiana Lameu, Helio Miranda Costa Junior, Robson Coutinho-Silva, Henning Ulrich
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:c025ea30d9a64a098e97483c9e8293de2021-11-18T08:20:45ZModulation of mouse embryonic stem cell proliferation and neural differentiation by the P2X7 receptor.1932-620310.1371/journal.pone.0096281https://doaj.org/article/c025ea30d9a64a098e97483c9e8293de2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24798220/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Novel developmental functions have been attributed to the P2X7 receptor (P2X7R) including proliferation stimulation and neural differentiation. Mouse embryonic stem cells (ESC), induced with retinoic acid to neural differentiation, closely assemble processes occurring during neuroectodermal development of the early embryo.<h4>Principal findings</h4>P2X7R expression together with the pluripotency marker Oct-4 was highest in undifferentiated ESC. In undifferentiated cells, the P2X7R agonist Bz-ATP accelerated cell cycle entry, which was blocked by the specific P2X7R inhibitor KN-62. ESC induced to neural differentiation with retinoic acid, reduced Oct-4 and P2X7R expression. P2X7R receptor-promoted intracellular calcium fluxes were obtained at lower Bz-ATP ligand concentrations in undifferentiated and in neural-differentiated cells compared to other studies. The presence of KN-62 led to increased number of cells expressing SSEA-1, Dcx and β3-tubulin, as well as the number of SSEA-1 and β3-tubulin-double-positive cells confirming that onset of neuroectodermal differentiation and neuronal fate determination depends on suppression of P2X7R activity. Moreover, an increase in the number of Ki-67 positive cells in conditions of P2X7R inhibition indicates rescue of progenitors into the cell cycle, augmenting the number of neuroblasts and consequently neurogenesis.<h4>Conclusions</h4>In embryonic cells, P2X7R expression and activity is upregulated, maintaining proliferation, while upon induction to neural differentiation P2X7 receptor expression and activity needs to be suppressed.Talita GlaserSophia La Banca de OliveiraArquimedes ChefferRenata BecoPatrícia MartinsMaynara FornazariClaudiana LameuHelio Miranda Costa JuniorRobson Coutinho-SilvaHenning UlrichPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e96281 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Talita Glaser
Sophia La Banca de Oliveira
Arquimedes Cheffer
Renata Beco
Patrícia Martins
Maynara Fornazari
Claudiana Lameu
Helio Miranda Costa Junior
Robson Coutinho-Silva
Henning Ulrich
Modulation of mouse embryonic stem cell proliferation and neural differentiation by the P2X7 receptor.
description <h4>Background</h4>Novel developmental functions have been attributed to the P2X7 receptor (P2X7R) including proliferation stimulation and neural differentiation. Mouse embryonic stem cells (ESC), induced with retinoic acid to neural differentiation, closely assemble processes occurring during neuroectodermal development of the early embryo.<h4>Principal findings</h4>P2X7R expression together with the pluripotency marker Oct-4 was highest in undifferentiated ESC. In undifferentiated cells, the P2X7R agonist Bz-ATP accelerated cell cycle entry, which was blocked by the specific P2X7R inhibitor KN-62. ESC induced to neural differentiation with retinoic acid, reduced Oct-4 and P2X7R expression. P2X7R receptor-promoted intracellular calcium fluxes were obtained at lower Bz-ATP ligand concentrations in undifferentiated and in neural-differentiated cells compared to other studies. The presence of KN-62 led to increased number of cells expressing SSEA-1, Dcx and β3-tubulin, as well as the number of SSEA-1 and β3-tubulin-double-positive cells confirming that onset of neuroectodermal differentiation and neuronal fate determination depends on suppression of P2X7R activity. Moreover, an increase in the number of Ki-67 positive cells in conditions of P2X7R inhibition indicates rescue of progenitors into the cell cycle, augmenting the number of neuroblasts and consequently neurogenesis.<h4>Conclusions</h4>In embryonic cells, P2X7R expression and activity is upregulated, maintaining proliferation, while upon induction to neural differentiation P2X7 receptor expression and activity needs to be suppressed.
format article
author Talita Glaser
Sophia La Banca de Oliveira
Arquimedes Cheffer
Renata Beco
Patrícia Martins
Maynara Fornazari
Claudiana Lameu
Helio Miranda Costa Junior
Robson Coutinho-Silva
Henning Ulrich
author_facet Talita Glaser
Sophia La Banca de Oliveira
Arquimedes Cheffer
Renata Beco
Patrícia Martins
Maynara Fornazari
Claudiana Lameu
Helio Miranda Costa Junior
Robson Coutinho-Silva
Henning Ulrich
author_sort Talita Glaser
title Modulation of mouse embryonic stem cell proliferation and neural differentiation by the P2X7 receptor.
title_short Modulation of mouse embryonic stem cell proliferation and neural differentiation by the P2X7 receptor.
title_full Modulation of mouse embryonic stem cell proliferation and neural differentiation by the P2X7 receptor.
title_fullStr Modulation of mouse embryonic stem cell proliferation and neural differentiation by the P2X7 receptor.
title_full_unstemmed Modulation of mouse embryonic stem cell proliferation and neural differentiation by the P2X7 receptor.
title_sort modulation of mouse embryonic stem cell proliferation and neural differentiation by the p2x7 receptor.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/c025ea30d9a64a098e97483c9e8293de
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