| Full text | |
| Author(s): Show less - |
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]
Total Authors: 15
|
| Affiliation: | [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
Total Affiliations: 7
|
| Document type: | Journal article |
| Source: | MOLECULAR PSYCHIATRY; v. 26, n. 6, p. 2633-2650, JUN 2021. |
| Web of Science Citations: | 11 |
| Abstract | |
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) | |
| FAPESP's process: | 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases |
| Grantee: | Alexander Henning Ulrich |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 15/13345-1 - Huntington's disease: Huntingtin roles during cell fate decision |
| Grantee: | Talita Glaser |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 12/50880-4 - Stem cells: from basic studies of kinin and purinergic receptor roles towards therapeutical applications |
| Grantee: | Alexander Henning Ulrich |
| Support Opportunities: | Research Projects - Thematic Grants |