Date of Award

2008

Degree Type

Thesis

Degree Name

Master of Science

Program

Biochemistry

Supervisor

Dr. Victor Han

Second Advisor

Dr. Thomas Drysdale

Third Advisor

Dr. Richard Rozmahel

Abstract

The main objective of this thesis was to identify the role(s) of IGF-I and IGF-II on the fate of mouse trophoblast stem cells (TS cells) and their role in contributing to the stem cell fate, when grown in the absence of additional growth factors. By analyzing the expression of self-renewal and trophoblast-specific transcription factors, the addition of IGF-I and IGF-II restored nuclear OCT4 and CDX2 expression, with IGF- II inducing a longer effect, while the expression of SOX2 was not restored. IGF-I was found to induce the differentiation of TS cells based on expression and quantitative analysis of PL-1 expression. Annexin-V and TUNEL staining demonstrated that IGF-II protects TS cells from cell death. The addition of FGF-4 to the system did not have an additive effect of protection and induced further negative effect when combined with IGFs. These studies demonstrate that IGF-I and IGF-II, have different biological effects on the fate of mouse TS cells, likely through different signal transduction pathways.

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