Journal article
J. Cha, X. Tong, E. Walker, T. Dahan, Veronica Cochrane, Sudipta Ashe, Ronan Russell, Anna B. Osipovich, Alex M. Mawla, M. Guo, Jin-hua Liu, M. Huising, M. Magnuson, M. Hebrok, Y. Dor, R. Stein
bioRxiv, 2022
bioRxiv, 2022
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APA
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Cha, J., Tong, X., Walker, E., Dahan, T., Cochrane, V., Ashe, S., … Stein, R. (2022). Species-specific roles for the MAFA and MAFB transcription factors in regulating islet β cell identity. BioRxiv.
Chicago/Turabian
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Cha, J., X. Tong, E. Walker, T. Dahan, Veronica Cochrane, Sudipta Ashe, Ronan Russell, et al. “Species-Specific Roles for the MAFA and MAFB Transcription Factors in Regulating Islet β Cell Identity.” bioRxiv (2022).
MLA
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Cha, J., et al. “Species-Specific Roles for the MAFA and MAFB Transcription Factors in Regulating Islet β Cell Identity.” BioRxiv, 2022.
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@article{j2022a,
title = {Species-specific roles for the MAFA and MAFB transcription factors in regulating islet β cell identity},
year = {2022},
journal = {bioRxiv},
author = {Cha, J. and Tong, X. and Walker, E. and Dahan, T. and Cochrane, Veronica and Ashe, Sudipta and Russell, Ronan and Osipovich, Anna B. and Mawla, Alex M. and Guo, M. and Liu, Jin-hua and Huising, M. and Magnuson, M. and Hebrok, M. and Dor, Y. and Stein, R.}
}
Abstract
Type 2 diabetes (T2D) is associated with compromised identity of insulin-producing pancreatic islet beta (β) cells, characterized by inappropriate production of other islet cell-enriched hormones. Here we examined how hormone misexpression was influenced by the MAFA and MAFB transcription factors, closely related proteins that maintain islet cell function. Mice specifically lacking MafA in β cells demonstrated broad, population-wide changes in hormone gene expression with an overall gene signature closely resembling islet gastrin (Gast)-positive cells generated under conditions of chronic hyperglycemia and obesity. A human β cell line deficient in MAFB, but not one lacking MAFA, also produced a gastrin (GAST)-positive gene expression pattern. In addition, GAST was detected in human T2D β cells with low levels of MAFB. Moreover, evidence is provided that human MAFB can directly repress GAST gene transcription. These results support a novel, species-specific role for MafA and MAFB in maintaining adult mouse and human β cell identity, respectively, by repressing expression of Gast/GAST and other non-β cell hormones.