| Texto completo | |
| Autor(es): Mostrar menos - |
Glaser, Talita
[1]
;
Shimojo, Hiromi
[2, 3]
;
Ribeiro, Deidiane Elisa
[1]
;
Martins, Patricia Pereira Lopes
[1]
;
Beco, Renata Pereira
[1]
;
Kosinski, Michal
[4, 5, 6, 7]
;
Sampaio, Vanessa Fernandes Arnaud
[1]
;
Correa-Velloso, Juliana
[1]
;
Oliveira-Giacomelli, Agatha
[1]
;
Lameu, Claudiana
[1]
;
de Jesus Santos, Ana Paula
[1]
;
de Souza, Hellio Danny Nobrega
[1]
;
Teng, Yang D.
[4, 5, 6]
;
Kageyama, Ryoichiro
[2]
;
Ulrich, Henning
[1]
Número total de Autores: 15
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil
[2] Kyoto Univ, Inst Frontier Life & Med Sci, Kyoto - Japan
[3] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka - Japan
[4] Harvard Med Sch, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02115 - USA
[5] Harvard Med Sch, Spaulding Rehabil Hosp, Dept Neurosurg, Boston, MA 02115 - USA
[6] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 - USA
[7] Polish Acad Sci, Mossakowski Med Res Ctr, Translat Plataform Regenerat Med, Warsaw - Poland
Número total de Afiliações: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | MOLECULAR PSYCHIATRY; v. 26, n. 6, p. 2633-2650, JUN 2021. |
| Citações Web of Science: | 11 |
| Resumo | |
Calcium, the most versatile second messenger, regulates essential biology including crucial cellular events in embryogenesis. We investigated impacts of calcium channels and purinoceptors on neuronal differentiation of normal mouse embryonic stem cells (ESCs), with outcomes being compared to those of in vitro models of Huntington's disease (HD). Intracellular calcium oscillations tracked via real-time fluorescence and luminescence microscopy revealed a significant correlation between calcium transient activity and rhythmic proneuronal transcription factor expression in ESCs stably expressing ASCL-1 or neurogenin-2 promoters fused to luciferase reporter genes. We uncovered that pharmacological manipulation of L-type voltage-gated calcium channels (VGCCs) and purinoceptors induced a two-step process of neuronal differentiation. Specifically, L-type calcium channel-mediated augmentation of spike-like calcium oscillations first promoted stable expression of ASCL-1 in differentiating ESCs, which following P2Y2 purinoceptor activation matured into GABAergic neurons. By contrast, there was neither spike-like calcium oscillations nor responsive P2Y2 receptors in HD-modeling stem cells in vitro. The data shed new light on mechanisms underlying neurogenesis of inhibitory neurons. Moreover, our approach may be tailored to identify pathogenic triggers of other developmental neurological disorders for devising targeted therapies. (AU) | |
| Processo FAPESP: | 18/07366-4 - Receptores de purinas e cininas como alvos de estudo e intervenção terapêutica em doenças neurológicas |
| Beneficiário: | Alexander Henning Ulrich |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 10/50554-4 - Modulação da diferenciação neuronal de células tronco embrionárias transientes de cálcio intracelulares e ativação de receptores purinérgicos |
| Beneficiário: | Talita Glaser |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 15/13345-1 - Doença de Huntington: envolvimento de Huntingtin no controle do comprometimento celular |
| Beneficiário: | Talita Glaser |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 12/50880-4 - Células-tronco: dos papéis de receptores de cininas e purinas às aplicações terapêuticas |
| Beneficiário: | Alexander Henning Ulrich |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |