Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. Rennian Wang

Abstract

Aldehyde dehydrogenase (ALDH) is an enzyme that regulates differentiation during pancreatic development, but determining the role of ALDH during endocrine differentiation is not well defined. The purpose of this study was to characterize transcription factors (TFs) and putative stem cell surface markers in ALDHhi or ALDHlo populations of the human fetal pancreas (18-22 weeks of age), and examine their expansion and differentiation in vitro and in vivo. Cell surface marker analysis demonstrated high co-localization of the stem cell marker CD133 with ALDHhi cells. ALDHhi cells also contained higher expression of islet- associated TFs and insulin. Expansion of sorted ALDHhi cells resulted in down-regulation of endocrine TFs genes, yet differentiated ALDHhi islet-like clusters partially restored TFs mRNA, but not protein levels. Sorted cell transplantation within fibrin matrix showed increased vascularization occurred with ALDHlo populations. In summary, this study demonstrated that ALDHhi cells represent an endocrine progenitor pool important for β-cell differentiation.


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