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| Status |
Public on Aug 18, 2010 |
| Title |
A small molecule accelerates neuronal differentiation in the adult rat |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Adult neurogenesis occurs in mammals and provides a mechanism for continuous neural plasticity in the brain.However, little is known about the molecular mechanisms regulating hippocampal neural progenitor cells (NPCs) and whether their fate can be pharmacologically modulated to improve neural plasticity and regeneration. Here, we report the characterization of a unique small molecule (KHS101) that selectively induces a neuronal differentiation phenotype. Mechanism of action studies revealed a link of KHS101 to cell cycle exit and specific binding to the TACC3 protein, whose knockdown in NPCs recapitulates the KHS101-induced phenotype. Upon systemic administration, KHS101 distributed to the brainandresulted in a significant increase in neuronal differentiation in vivo. Our findings indicate that KHS101 accelerates neuronal differentiation by interaction with TACC3 and may provide a basis for pharmacological intervention.directed at endogenous NPCs.
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| Overall design |
Compare expression profile of KHS101-treated hippocampal progenitor cells (2 concentrations) vs. DMSO (negative control), retinoic acid (positive control)
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| Contributor(s) |
Wurdak H, Zhu S, Min KH, Aimone L, Lairson LL, Watson J, Chopiuk G, Demas J, Charette B, Weerapana E, Cravatt BF, Cline HT, Peters EC, Zhang J, Walker JR, Wu C, Chang J, Tuntland T, Cho CY, Schultz PG |
| Citation(s) |
20823227 |
| Submission date |
Aug 17, 2010 |
| Last update date |
Jul 31, 2017 |
| Contact name |
John R Walker |
| E-mail(s) |
jwalker@gnf.org
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| Phone |
858-812-1636
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| Organization name |
Genomics Institute of the Novartis Research Foundation
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| Lab |
Genetics Core
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| Street address |
10675 John Jay Hopkins
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| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92121 |
| Country |
USA |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA130815 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23668_RAW.tar |
17.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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