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Dissertation/Thesis Abstract

Aberrant Stem Cell Differentiation in Mutant EpCAM Mice
by Rabalais, John Paul-Nguyen, M.S., University of California, San Diego, 2019, 35; 13896573
Abstract (Summary)

Congenital Tufting Enteropathy (CTE) is a rare intestinal disease which presents in newborns, causing intestinal failure and failure to thrive. Mutations in EpCAM, Epithelial Cell Adhesion Molecule, have been shown to be causative in CTE. In addition to its role in mediating cell adhesion, EpCAM has also been linked to cell proliferation and differentiation. In this project, we investigated the role of EPCAM mutation on intestinal epithelial cell differentiation in the small intestine. To do so, adult inducible EpCAMΔ4/Δ4 mice were used to investigate these changes. We found there to be severe decreases in secretory lineages (Paneth, goblet, enteroendocrine) in mutant mice along with characteristic tufting of the villi. We also noted changes in differentiation factor levels via qPCR and immunoblotting. Atoh1 was decreased at both the RNA and protein levels, along with a decrease in Klf4, which is implicated in terminal goblet cell differentiation, at the RNA level. We also discovered increased NOTCH1 signaling via immunoblot, which activates the enterocyte differentiation pathway. Therefore, we conclude that in the presence of mutated EpCAM, there is improper differentiation signaling upon intestinal stem cells leading to a reduction in secretory cell lineages.

Indexing (document details)
Advisor: Sivagnanam, Mamata
Commitee: Forbes, Douglass, Mel, Stephanie
School: University of California, San Diego
Department: Biology
School Location: United States -- California
Source: MAI 81/3(E), Masters Abstracts International
Subjects: Biology
Keywords: Differentiation, EpCAM, Intestines
Publication Number: 13896573
ISBN: 9781088336816
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