ATP and spontaneous calcium oscillations control neural stem cell fate determination in Huntington’s disease: a novel approach for cell clock research
| Autor: | Deidiane Elisa Ribeiro, Juliana Corrêa-Velloso, Patrícia Pereira Lopes Martins, Talita Glaser, Ryoichiro Kageyama, Hiromi Shimojo, Vanessa Fernandes Arnaud Sampaio, Renata Beco, Henning Ulrich, Claudiana Lameu, Ana Paula Santos, Yang D. Teng, Ágatha Oliveira-Giacomelli, Hellio Danny Nóbrega de Souza, Michal Kosinski |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Voltage-dependent calcium channel Purinergic receptor Neurogenesis NEUROCIÊNCIAS chemistry.chemical_element Calcium Embryonic stem cell Neural stem cell Calcium in biology Cell biology 03 medical and health sciences Cellular and Molecular Neuroscience Psychiatry and Mental health 030104 developmental biology 0302 clinical medicine chemistry Second messenger system Molecular Biology 030217 neurology & neurosurgery |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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