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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 15, 2016 |
| Title |
Artemisinins target GABAA receptor signaling and impair alpha cell identity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Type 1 diabetes is characterized by the destruction of pancrea tic beta cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types including glucagon-producing alpha cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of alpha cells to functional beta-like cells. Here we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm. We show that the protein gephyrin is the mammalian target of these antimalaria drugs, and that enhancement of GABAA receptor signaling contributes to the mechanism of action of these molecules in pancreatic transdifferentiation. Our results in zebrafish, rodents and primary human pancreatic islets indicate that gephyrin is a novel druggable target for the regeneration of pancreatic beta cell mass from alpha cells.
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| Overall design |
There are two parts in the transcriptional study on mouse cell lines in this project. One part is on Min6-ARX inducible cells with different induction time of Dox. This is done in three different clones. The other part is on alpha-TC1 cells. This is done in one concentration of Artemether, one time point and two biological repeats.
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| Contributor(s) |
Li J, Kubicek S |
| Citation(s) |
27916275 |
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| Submission date |
Jul 19, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Jin Li |
| E-mail(s) |
jli21@bidmc.harvard.edu
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| Organization name |
BIDMC
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| Street address |
Blackfan 3
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| City |
Boston |
| ZIP/Postal code |
02134 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA330538 |
| SRA |
SRP078950 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE84592_RAW.tar |
1.6 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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