Analysis of Directed Differentiation Strategies for the Derivation of Endocrine Pancreas from Embryonic Stem Cells

Date of Completion

January 2011

Keywords

Biology, Molecular|Biology, Genetics|Biology, Endocrinology

Degree

Ph.D.

Abstract

The success of pancreatic islet transplantation to treat Type I diabetes mellitus has been limited by the availability of patient-matched islets for transplant, and by the need for lifelong recipient maintenance on immunosuppressive medications. Both of these difficulties could be overcome by the derivation of pancreatic islets from patient-derived pluripotent stem cells. Research pursued in this proposal investigates strategies for the generation and analysis of pancreatic lineages derived from stem cells. This study in regenerative biology serves to contribute to the directed differentiation of embryonic stem cell-derived endocrine pancreas structures with the capacity to function and serve as substitute endocrine islets for use in future cellular therapeutics to treat Type I diabetic patients. This thesis reports on the development of a single-cell transcript analysis technique to identify individual cell types in complex embryonic stem cell cultures, the derivation of a definitive endoderm progenitor population from embryonic stem cells to assist with directed protocols for generating endocrine pancreas, and investigation of properly timed expression of the master endocrine pancreas regulator Ngn3 to promote ES cell differentiation toward a pancreatic fate and enhance endocrine pancreas hormone-expressing cell type maturation. ^

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