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
	Freja Louise Nielsen PhD student
	Magnus Stenderup Bjerre MSc 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.