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题目:: Quantitative-proteomic comparison of alpha and Beta cells to uncover novel targets for lineage reprogramming.
作者:: 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)
状态:: 发布时间2014-04-24 , 更新时间 2015-08-06
期刊:: PLoS One
摘要:: 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.
语言:: eng
DOI:

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