P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord
The ependyma of the spinal cord is a latent stem cell niche that is reactivated by injury, generating new cells that migrate to the lesion site to limit the damage. The mechanisms by which ependymal cells are reactivated after injury remain poorly understood. ATP has been proposed to act as a diffus...
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| フォーマット: | article |
| 言語: | 英語 |
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2023
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| オンライン･アクセス: | https://hdl.handle.net/20.500.12381/3939 https://doi.org/10.3389/fncel.2023.1288676 |
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| _version_ | 1868890192804315136 |
|---|---|
| author | Falco, María Victoria |
| author2 | Fabbiani, María Gabriela Maciel, Cecilia Valdivia, Spring Vitureira, Nathalia Russo, Raúl E. |
| author2_role | author author author author author |
| author_browse | Fabbiani, María Gabriela Falco, María Victoria Maciel, Cecilia Russo, Raúl E. Valdivia, Spring Vitureira, Nathalia |
| author_facet | Falco, María Victoria Fabbiani, María Gabriela Maciel, Cecilia Valdivia, Spring Vitureira, Nathalia Russo, Raúl E. |
| author_role | author |
| collection | IIBCE en REDI |
| dc.creator.none.fl_str_mv | Falco, María Victoria Fabbiani, María Gabriela Maciel, Cecilia Valdivia, Spring Vitureira, Nathalia Russo, Raúl E. |
| dc.date.none.fl_str_mv | 2023-12-18 2025-04-22T14:22:42Z 2025-04-22T14:22:42Z |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/20.500.12381/3939 FCE_3_2022_1_172524 https://doi.org/10.3389/fncel.2023.1288676 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Frontiers |
| dc.relation.none.fl_str_mv | https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2023.1288676/full https://hdl.handle.net/20.500.12381/3934 https://hdl.handle.net/20.500.12381/3935 https://hdl.handle.net/20.500.12381/3936 https://hdl.handle.net/20.500.12381/3937 https://hdl.handle.net/20.500.12381/3938 https://hdl.handle.net/20.500.12381/4014 https://hdl.handle.net/20.500.12381/3951 https://hdl.handle.net/20.500.12381/5145 https://hdl.handle.net/20.500.12381/5248 https://hdl.handle.net/20.500.12381/5333 https://hdl.handle.net/20.500.12381/5345 |
| dc.rights.none.fl_str_mv | Acceso abierto info:eu-repo/semantics/openAccess Reconocimiento 4.0 Internacional. (CC BY) |
| dc.source.none.fl_str_mv | Frontiers in Cellular Neuroscience reponame:IIBCE en REDI instname:Instituto de Investigaciones Biológicas Clemente Estable instacron:Instituto de Investigaciones Biológicas Clemente Estable |
| dc.subject.none.fl_str_mv | Médula espinal Lesión Células madre Ciencias Médicas y de la Salud Medicina Básica Neurociencias |
| dc.title.none.fl_str_mv | P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article Publicado info:eu-repo/semantics/publishedVersion |
| description | The ependyma of the spinal cord is a latent stem cell niche that is reactivated by injury, generating new cells that migrate to the lesion site to limit the damage. The mechanisms by which ependymal cells are reactivated after injury remain poorly understood. ATP has been proposed to act as a diffusible “danger signal” to alert about damage and start repair. Indeed, spinal cord injury (SCI) generates an increase in extracellular ATP around the lesion epicenter that lasts for several hours and affects the functional outcome after the damage. The P2X7 receptor (P2X7r) has functional properties (e.g., low sensitivity for ATP, high permeability for Ca2+) that makes it a suitable candidate to act as a detector of tissue damage. Because ependymal cells express functional P2X7r that generate an inward current and regenerative Ca2+ waves, we hypothesize that the P2X7r has a main role in the mechanisms by which progenitor-like cells in the ependyma react to tissue damage. To test this possibility, we simulated the P2X7r activation that occurs after SCI by in vivo intraspinal injection of the selective agonist BzATP nearby the central canal. We found that BzATP rescued ependymal cells from quiescence by triggering a proliferative response similar to that generated by injury. In addition, P2X7r activation by BzATP induced a shift of ependymal cells to a glial fibrillary acidic protein (GFAP) phenotype similar to that induced by injury. However, P2X7r activation did not trigger the migration of ependyma-derived cells as occurs after tissue damage. Injection of BzATP induced the expression of connexin 26 (Cx26) in ependymal cells, an event needed for the proliferative reaction after injury. BzATP did not induce these changes in ependymal cells of P2X7–/– mice supporting a specific action on P2X7r. In vivo blockade of P2X7r with the potent antagonist AZ10606120 reduced significantly the injury-induced proliferation of ependymal cells. Our data indicate that P2X7r has a key role in the “awakening” of the ependymal stem cell niche after injury and suggest purinergic signaling is an interesting target to improve the contribution of endogenous progenitors to repair. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_cb276edc2d56d9652006fa5f3e92e3d8 |
| identifier_str_mv | FCE_3_2022_1_172524 |
| instacron_str | Instituto de Investigaciones Biológicas Clemente Estable |
| institution | Instituto de Investigaciones Biológicas Clemente Estable |
| instname_str | Instituto de Investigaciones Biológicas Clemente Estable |
| language | eng |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:redi.anii.org.uy:20.500.12381/3939 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher.none.fl_str_mv | Frontiers |
| reponame_str | IIBCE en REDI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Acceso abierto Reconocimiento 4.0 Internacional. (CC BY) |
| spelling | P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cordFalco, María VictoriaFabbiani, María GabrielaMaciel, CeciliaValdivia, SpringVitureira, NathaliaRusso, Raúl E.Médula espinalLesiónCélulas madreCiencias Médicas y de la SaludMedicina BásicaNeurocienciasThe ependyma of the spinal cord is a latent stem cell niche that is reactivated by injury, generating new cells that migrate to the lesion site to limit the damage. The mechanisms by which ependymal cells are reactivated after injury remain poorly understood. ATP has been proposed to act as a diffusible “danger signal” to alert about damage and start repair. Indeed, spinal cord injury (SCI) generates an increase in extracellular ATP around the lesion epicenter that lasts for several hours and affects the functional outcome after the damage. The P2X7 receptor (P2X7r) has functional properties (e.g., low sensitivity for ATP, high permeability for Ca2+) that makes it a suitable candidate to act as a detector of tissue damage. Because ependymal cells express functional P2X7r that generate an inward current and regenerative Ca2+ waves, we hypothesize that the P2X7r has a main role in the mechanisms by which progenitor-like cells in the ependyma react to tissue damage. To test this possibility, we simulated the P2X7r activation that occurs after SCI by in vivo intraspinal injection of the selective agonist BzATP nearby the central canal. We found that BzATP rescued ependymal cells from quiescence by triggering a proliferative response similar to that generated by injury. In addition, P2X7r activation by BzATP induced a shift of ependymal cells to a glial fibrillary acidic protein (GFAP) phenotype similar to that induced by injury. However, P2X7r activation did not trigger the migration of ependyma-derived cells as occurs after tissue damage. Injection of BzATP induced the expression of connexin 26 (Cx26) in ependymal cells, an event needed for the proliferative reaction after injury. BzATP did not induce these changes in ependymal cells of P2X7–/– mice supporting a specific action on P2X7r. In vivo blockade of P2X7r with the potent antagonist AZ10606120 reduced significantly the injury-induced proliferation of ependymal cells. Our data indicate that P2X7r has a key role in the “awakening” of the ependymal stem cell niche after injury and suggest purinergic signaling is an interesting target to improve the contribution of endogenous progenitors to repair.Wings for Life, Spinal Cord Research FoundationMorton Cure Paralysis FundAgencia Nacional de Investigación e InnovaciónFrontiers2025-04-22T14:22:42Z2025-04-22T14:22:42Z2023-12-18Artículoinfo:eu-repo/semantics/articlePublicadoinfo:eu-repo/semantics/publishedVersionhttps://hdl.handle.net/20.500.12381/3939FCE_3_2022_1_172524https://doi.org/10.3389/fncel.2023.1288676Frontiers in Cellular Neurosciencereponame:IIBCE en REDIinstname:Instituto de Investigaciones Biológicas Clemente Estableinstacron:Instituto de Investigaciones Biológicas Clemente Estableenghttps://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2023.1288676/fullhttps://hdl.handle.net/20.500.12381/3934https://hdl.handle.net/20.500.12381/3935https://hdl.handle.net/20.500.12381/3936https://hdl.handle.net/20.500.12381/3937https://hdl.handle.net/20.500.12381/3938https://hdl.handle.net/20.500.12381/4014https://hdl.handle.net/20.500.12381/3951https://hdl.handle.net/20.500.12381/5145https://hdl.handle.net/20.500.12381/5248https://hdl.handle.net/20.500.12381/5333https://hdl.handle.net/20.500.12381/5345Acceso abiertoinfo:eu-repo/semantics/openAccessReconocimiento 4.0 Internacional. (CC BY)oai:redi.anii.org.uy:20.500.12381/39392026-06-16T05:25:28Z |
| spellingShingle | P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord Falco, María Victoria Médula espinal Lesión Células madre Ciencias Médicas y de la Salud Medicina Básica Neurociencias |
| status_str | publishedVersion |
| title | P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord |
| title_full | P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord |
| title_fullStr | P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord |
| title_full_unstemmed | P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord |
| title_short | P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord |
| title_sort | P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord |
| topic | Médula espinal Lesión Células madre Ciencias Médicas y de la Salud Medicina Básica Neurociencias |
| url | https://hdl.handle.net/20.500.12381/3939 https://doi.org/10.3389/fncel.2023.1288676 |