In this project, the Mandrup Group investigates the transcriptional plasticity of pancreatic islet cells with a focus on the insulin-producing β-cells. Several lines of evidence indicate that prolonged nutrient overload not only stimulates insulin secretion but also reprograms the genome of pancreatic β-cells. Initially, this helps the β-cells to adapt to the increased demand for insulin by promoting β-cell capacity and proliferation, but this may also drive β-cell dedifferentiation and failure, which may eventually result in type 2 diabetes mellitus. We investigate the early adaptive transcriptional responses of the endocrine pancreas to dietary challenges. Furthermore, we study the transcriptional and epigenetic mechanisms leading to postnatal β-cell maturation, a process that may be partly reversed in diabetes.

Technologies: We use advanced mouse models, isolated islets from mice and humans and islet model systems. We apply sequencing- and bioimaging-based single cell technologies combined with a suite of additional functional genomics technologies and computational approaches.  

This project is supported by a grant from The Novo Nordisk Foundation.

People involved

	Lasse Lehtonen Postdoc
	Isabell Victoria Strandby Ernst PhD student
	Freja Louise Nielsen PhD student
	Magnus Stenderup Bjerre Project student

Relevant publications

J.G.S. Madsen*, A. Rauch*, E.L. Van Hauwaert, S.F. Schmidt, M. Winnefeld, S. Mandrup (2018) Integrated analysis of motif activity and gene expression changes of transcription factors. Genome Res. 28, 243-255.

S.F. Schmidt*, J.G.S. Madsen*, K. Østerli, L.L.C. Poulsen, Sofia Salö, M. Børgesen, A. Loft, R. Nielsen, J.J.Holst, Louise T. Dalgaard, S. Mandrup (2016) Integrative genomics outlines a biphasic glucose response and a ChREBP-RORgamma axis regulating proliferation in β-cells. Cell Reports 16, 2359-2372.