Quantitative-Proteomic Comparison of Alpha and Beta Cells to Uncover Novel Targets for Lineage Reprogramming

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Quantitative-Proteomic Comparison of Alpha and Beta Cells to Uncover Novel Targets for Lineage Reprogramming

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Title: Quantitative-Proteomic Comparison of Alpha and Beta Cells to Uncover Novel Targets for Lineage Reprogramming
Author: Choudhary, Amit; Hu He, Kaihui; Mertins, Philipp; Udeshi, Namrata D.; Dančík, Vlado; Fomina-Yadlin, Dina; Kubicek, Stefan; Clemons, Paul A.; Schreiber, Stuart L.; Carr, Steven A.; Wagner, Bridget K.

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Citation: Choudhary, A., K. Hu He, P. Mertins, N. D. Udeshi, V. Dančík, D. Fomina-Yadlin, S. Kubicek, et al. 2014. “Quantitative-Proteomic Comparison of Alpha and Beta Cells to Uncover Novel Targets for Lineage Reprogramming.” PLoS ONE 9 (4): e95194. doi:10.1371/journal.pone.0095194. http://dx.doi.org/10.1371/journal.pone.0095194.
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Abstract: Type-1 diabetes (T1D) is an autoimmune disease in which insulin-secreting pancreatic beta cells are destroyed by the immune system. An emerging strategy to regenerate beta-cell mass is through transdifferentiation of pancreatic alpha cells to beta cells. We previously reported two small molecules, BRD7389 and GW8510, that induce insulin expression in a mouse alpha cell line and provide a glimpse into potential intermediate cell states in beta-cell reprogramming from alpha cells. These small-molecule studies suggested that inhibition of kinases in particular may induce the expression of several beta-cell markers in alpha cells. To identify potential lineage reprogramming protein targets, we compared the transcriptome, proteome, and phosphoproteome of alpha cells, beta cells, and compound-treated alpha cells. Our phosphoproteomic analysis indicated that two kinases, BRSK1 and CAMKK2, exhibit decreased phosphorylation in beta cells compared to alpha cells, and in compound-treated alpha cells compared to DMSO-treated alpha cells. Knock-down of these kinases in alpha cells resulted in expression of key beta-cell markers. These results provide evidence that perturbation of the kinome may be important for lineage reprogramming of alpha cells to beta cells.
Published Version: doi:10.1371/journal.pone.0095194
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997365/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12152899
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