Poster Session 1 - E13
1,2,3Frankie Poon, 1,2,3Roman Korytnikov, 1,2,3Cristina Nostro
1 Toronto General Hospital Research Institute; 2 Department of Physiology, University of Toronto; 3 McEwen Centre for Regenerative Medicine
Type 1 diabetic patients suffer from glucose dysregulation due to the lack of insulin-producing β-cells. By using human pluripotent stem cells (hPSCs), we can potentially generate an infinite source of transplant suitable β-like cells for these patients. This process relies heavily on cytokines and small molecules to recapitulate signaling pathways occurring during pancreas development. To ensure the efficiency and safety of these hPSC derivatives, it is crucial to understand the molecular mechanisms driving lineage specification. Our lab previously described that treatment with nicotinamide (NA), Noggin and Epidermal growth factor (EGF) during patterning of the PDX1+ endoderm induce efficient expression of NKX6-1. This effect is synergistic and necessary for the generation of cells co-expressing NKX6-1 and PDX1. However, the mechanisms controlling NKX6-1 upregulation remain elusive and determining whether co-expression of PDX1 and NKX6-1 locks cells to the pancreatic fate has yet to be evaluated. In this study, we performed a small molecule screen aimed at identifying molecules that can effectively induce NKX6-1 expression and compare the developmental potential of putative pancreatic progenitors generated using alternative approaches. Ultimately, understanding the key pathways regulating pancreatic lineage commitment will define the molecular mechanisms leading to fate determination and provide a blueprint for the effective generation of a cellular product for use in clinical settings.