SINGLE CELL RNASEQ OF
The islets are vital regulators of metabolism, but unbiased analysis of their cellular composition and gene regulatory networks at cell type specific level is lacking.
As a part of our larger effort to understand gene-regulation in normal and T2D islets we are mapping gene expression in transcriptionally defined cell types in human islets using single cell RNAseq. Cell-type specific gene expression will allow us to proceed with extraordinary precision and will lead to a major leap forward for understanding of islet biology and what fails in T2D. We have established a pipeline for single cell RNAseq of human islet cells and successfully sequenced >2000 cells from human donors. This resulted in a model comprising >10 distinct cell types, including cells expressing the major islet hormones. This model will be confirmed using multiple single molecule in situ hybridization and immunohistochemistry. In addition to sequencing more cells to resolve the rare populations and subpopulations, we address how our model is affected by T2D in terms of cell composition and gene-regulatory networks.
The project is a collaboration between the Wierup group and a laboratory at the fore front of single cell sequencing technology (http://www.hjerling-leffler-lab.org/) and has the potential to shift our understanding of the cellular basis for T2D.