From Liquid To Life: Reprogramming Urinary Stem Cells to Pancreatic Cells

Background: As of 2024, more than 250 Canadians alone die each year waiting for organ transplants (Canadian Blood Services, 2024). The ability to efficiently differentiate urinary stem cells into pancreatic cells, and form organoids sparks an optimistic approach for patients with diabetes who otherwise require insulin injections on a regular basis. Objective: Aim of the study was to identify highly specific transcription factors that play crucial roles in maintenance of cell fate, and promote stage specific differentiation from urinary stem cells to functional pancreatic beta cells. Methodology: Data mining and literature review allowed for the identification of transcription factors and supporting proteins involved in the differentiation of pancreatic beta cells. These were further refined via analysis of several databases (KEGG, Pathway Commons). NCBI Gene Database was also utilized to determine pancreas tissue specificity for each protein identified. Cytoscape (version 3.10.0) enabled visualization of molecular pathways/gene interactions through different stages of differentiation along with a hierarchical cluster analysis. Subsequent enrichment analysis was conducted on the identified transcription factors and associated proteins using StringAPP (version 2.0.3), facilitating protein-protein interactome analysis. Results/Implications: In this pilot study, with findings from Cytoscape and enrichment analysis, novel transcription factors involved in reprogramming of pancreatic beta cells were identified with high statistical confidence. Both transcription factors and supporting ECM proteins were grouped in distinct stages of pancreatic differentiation. Overall, the current study addresses the need of identifying highly specific and efficient differentiation factors essential for successful reprogramming of patient-derived stem cells into pancreatic beta cells.