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Series GSE84714 Query DataSets for GSE84714
Status Public on Jan 19, 2017
Title Artemisinins target GABA receptor signaling to induce alpha to beta cell transdifferentiation
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Type 1 diabetes is characterized by the destruction of pancreatic 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, overexpression of the master regulatory transcription factor Pax4 or loss of its counterplayer Arx are sufficient to induce the conversion of alpha cells to functional beta-like cells. Here we identify artemisinins as small molecules that functionally repress Arx and induce beta-cell characteristics in alpha cells. We show that the protein gephyrin is the mammalian target of these antimalaria drugs. Finally, we demonstrate that gephyrin-mediated enhancement of GABAA receptor signaling is the mechanism of action of these molecules in pancreatic transdifferentiation. Our results indicate that gephyrin is a novel druggable target for the regeneration of pancreatic beta cell mass from alpha cells.
Overall design Transcriptional dissection of Artemether treated, human pancreatic islets of one donor using single-cell RNA-seq
Contributor(s) Li J, Frogne T, Courtney M, Huber KV, Sturtzel C, Casteels T, Lardeau C, Klughammer J, Farlik M, Sdelci S, Baburin I, Kimmel RA, Majek P, Pauler FM, Penz T, Stukalov A, Gridling M, Parapatics K, Barbieux C, Berishvili E, Spittler A, Colinge J, Bennett K, Meyer D, Hering S, Bock C, Distel M, Superti-Furga G, Collombat P, Hecksher-Sørensen J, Kubicek S
Citation(s) 27916275
Submission date Jul 22, 2016
Last update date May 15, 2019
Contact name Christoph Bock
Organization name CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Street address Lazarettgasse 14
City Vienna
ZIP/Postal code 1090
Country Austria
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (36)
GSM2248241 islet_single_cell_artemether_1
GSM2248242 islet_single_cell_artemether_2
GSM2248243 islet_single_cell_artemether_3
BioProject PRJNA330917
SRA SRP079357

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Supplementary file Size Download File type/resource
GSE84714_RAW.tar 222.0 Mb (http)(custom) TAR (of TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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