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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096281&type=printable |
| _version_ | 1826587251700662272 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T01:06:46Z |
| format | Article |
| id | doaj.art-c025ea30d9a64a098e97483c9e8293de |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T16:22:28Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c025ea30d9a64a098e97483c9e8293de2025-02-22T05:32:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9628110.1371/journal.pone.0096281Modulation of mouse embryonic stem cell proliferation and neural differentiation by the P2X7 receptor.Talita GlaserSophia La Banca de OliveiraArquimedes ChefferRenata BecoPatrícia MartinsMaynara FornazariClaudiana LameuHelio Miranda Costa JuniorRobson Coutinho-SilvaHenning Ulrich<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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096281&type=printable |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096281&type=printable |
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