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Title page for ETD etd-03172015-122924


Type of Document Dissertation
Author Poulin, Emily Jean
URN etd-03172015-122924
Title Characterization of Lrig1+ colonic stem/progenitor cells and their transformative capacity
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
Christopher Wright, D.Phil Committee Chair
Christopher Williams, M.D., Ph.D. Committee Member
Ethan Lee, M.D., Ph.D. Committee Member
William Tansey, Ph.D. Committee Member
Keywords
  • stem cells
  • Lrig1
Date of Defense 2015-02-11
Availability unrestricted
Abstract
The intestinal epithelium is a continuously renewing tissue. This rapid renewal is fueled by stem cells that reside in the base of the crypts of Lieberk├╝hn, the functional unit of the intestinal epithelium. The identity of intestinal stem cells has been the subject of over fifty years of ongoing investigation. Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1) marks a population of intestinal stem cells, but the identity of Lrig1+ cells has remained controversial due to discrepant reports of Lrig1 expression in the crypt base. We characterized two Lrig1+ populations in the colonic epithelium using two anti-Lrig1 antibodies and a new Lrig1 reporter mouse. We determined that these two populations could be distinguished by reporter expression, Lgr5 expression, and likely the glycosylation status of Lrig1. Since stem cells are widely considered to be tumor-initiating cells in colorectal cancer, we developed new mouse models of colonic neoplasia: Lrig1CreERT2/+;Apcfl/fl and Lrig1CreERT2/+;Apcfl/fl;KrasLSL-G12D/+. We found that Apc loss resulted in high-grade tumors; expression of mutant Kras expression did not significantly affect histological grade of tumors, but may contribute to increased invasion.
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