Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks

I Akerman, Z Tu, A Beucher, DM Rolando, C Sauty-Colace, M Benazra, N Nakic, J Yang, H Wang, L Pasquali, I Moran, J Garcia-Hurtado, N Castro, R Gonzalez-Franco, AF Stewart, C Bonner, L Piemonti, T Berney, L Groop, J Kerr-ConteF Pattou, C Argmann, E Schadt, P Ravassard, J Ferrer

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Abstract

Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)400-411
Number of pages12
JournalCell Metabolism
Volume25
Issue number2
DOIs
Publication statusPublished - 2017

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Akerman, I., Tu, Z., Beucher, A., Rolando, DM., Sauty-Colace, C., Benazra, M., Nakic, N., Yang, J., Wang, H., Pasquali, L., Moran, I., Garcia-Hurtado, J., Castro, N., Gonzalez-Franco, R., Stewart, AF., Bonner, C., Piemonti, L., Berney, T., Groop, L., ... Ferrer, J. (2017). Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks. Cell Metabolism, 25(2), 400-411. https://doi.org/10.1016/j.cmet.2016.11.016