Date of Award


Degree Type


Degree Name

Master of Science




Dr. Cheryle Séguin


Diabetes is becoming increasingly prevalent in North America, highlighting the necessity to create a renewable source of pancreatic P-cells for therapeutic purposes. The current study was undertaken to explore the hypothesis that ectopic expression of lineage­ determining transcription factors could generate a source of proliferative, homogenous pancreatic progenitor cells capable of subsequent differentiation to functional endocrine cell types, including P-cells. We validated transgenic systems for transgene delivery in HESC and subsequently generated and analyzed gene expression patterns in transgenic cell populations engineered to constitutively express pancreatic transcription factors PAX4, PDX1, or NGN3. We demonstrate that ectopic expression of either PAX4 or PDX1 is not sufficient to specify pancreatic cells from human embryonic stem cells or definitive endoderm cells. In contrast, ectopic NGN3 expression specifies pancreatic endocrine cells from definitive endoderm. In conclusion, this study provides proof of principle of the ability to generate pancreatic endocrine cells using transcription factor overexpression in human embryonic stem cells



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