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Neurogenin3 phosphorylation controls reprogramming efficiency of pancreatic ductal organoids into endocrine cells

Azzarelli, R; Rulands, S; Nestorowa, S; Davies, J; Campinoti, S; Gillotin, S; Bonfanti, P; ... Philpott, A; + view all (2018) Neurogenin3 phosphorylation controls reprogramming efficiency of pancreatic ductal organoids into endocrine cells. Scientific Reports , 8 , Article 15374. 10.1038/s41598-018-33838-5. Green open access

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Abstract

β-cell replacement has been proposed as an effective treatment for some forms of diabetes, and in vitro methods for β-cell generation are being extensively explored. A potential source of β-cells comes from fate conversion of exocrine pancreatic cells into the endocrine lineage, by overexpression of three regulators of pancreatic endocrine formation and β-cell identity, Ngn3, Pdx1 and MafA. Pancreatic ductal organoid cultures have recently been developed that can be expanded indefinitely, while maintaining the potential to differentiate into the endocrine lineage. Here, using mouse pancreatic ductal organoids, we see that co-expression of Ngn3, Pdx1 and MafA are required and sufficient to generate cells that express insulin and resemble β-cells transcriptome-wide. Efficiency of β-like cell generation can be significantly enhanced by preventing phosphorylation of Ngn3 protein and further augmented by conditions promoting differentiation. Taken together, our new findings underline the potential of ductal organoid cultures as a source material for generation of β-like cells and demonstrate that post-translational regulation of reprogramming factors can be exploited to enhance β-cell generation.

Type: Article
Title: Neurogenin3 phosphorylation controls reprogramming efficiency of pancreatic ductal organoids into endocrine cells
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-018-33838-5
Publisher version: http://dx.doi.org/10.1038/s41598-018-33838-5
Language: English
Additional information: © The Author(s) 2018O. pen Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/10060086
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