Transcriptional profiling and functional network analyses of islet-like clusters (ILCs) generated from pancreatic stem cells in vitro

• Pancreatic stem cell derived islets and native primary islets compared by microarray
• Inflammatory and EMT molecules upregulated
• Early β-cell/pancreatic markers upregulated and late stage markers downregulated
• Co-expression of mesenchymal markers seen
• In vitro generated pancreatic stem cell derived islets are immature.

We have earlier reported the generation of islet-like clusters (ILCs) from mesenchymal stromal cell (MSC)-like cells present in murine pancreas. Here we compare these ILCs to native primary islets by transcriptome screening. Genes were categorized into functional clusters and network analysis was done by Ingenuity Pathway Analysis (IPA). The fold changes for a selected panel of molecules were validated with quantitative real time PCR. A differential expression of 6516 genes (p-value ≤ 0.05, 1.5 fold change) with upregulated expression of numerous inflammatory and ‘Epithelial to Mesenchymal Transition’ molecules (EMT) was seen. A significant increase in the early β-cell marker expression in the ILCs indicated their progenitor status. Although not fully mature, ILCs offer certain advantages including the large number of easily inducible initiator MSCs. These ‘naïve’ cells may aid to devise protocols for generating functional islet equivalents. Moreover their maturation upon transplantation under local microenvironmental niche is highly possible.