Enzyme Ogt in Islet Development
Although the developing pancreas is exquisitely sensitive to nutrient supply in utero, it is not entirely clear how nutrient-driven post-translational modification of proteins impacts the pancreas during development. A group of researchers including MSI PI Emilyn Alejandro (assistant professor, Department of Integrative Biology and Physiology) has investigated the heretofore unknown role of the nutrient-sensing enzyme O-GlcNAc transferase (Ogt) in exocrine and endocrine islet development. They showed the first evidence that Ogt regulates pancreas development. The research included single cell RNA sequencing, which was analyzed by Dr. Ying Zhang, a member of MSI’s Research Informatics Solutions group. These findings underscore the requirement of O-GlcNAcylation during pancreas development and show that Ogt is essential for pancreatic progenitor survival, providing a novel mechanistic link between nutrients and pancreas development.
The research was published in the journal Development: D Baumann, A Wong, B Akhaphong, S Jo, S Pritchard, R Mohan, G Chung, Y Zhang, EU Alejandro. 2020. Role of nutrient-driven O-GlcNAc-post-translational modification in pancreatice exocrine and endocrine islet development. Development 147. doi: 10.1242/dev.186643.
Research Computing partners:
- Minnesota Supercomputing Institute
Image description: Single cell RNA sequencing analysis reveal cell type heterogeneity in OgtKOPanc pancreas. (A) Pancreases dissected at E15.5 were homogenized and flow sorted using a GFP reporter for Pdx1Cre expression in OgtKOPanc (or an anti-E-cadherin-GFP antibody for control cells), and run through a 10x Genomics single-cell RNAseq protocol (n=at least from three animals pooled per genotypes). t-distributed stochastic neighbor embedding (t-SNE) visualization from pooled E15.5 OgtKOPanc and control. (B) Dot plot representation of selected gene expression. Image and description, D Baumann, et al., Development 147 (2020), doi: 10.1242/dev.186643.
