Maher, Travis Joseph2011-05-102011-05-102011-02https://hdl.handle.net/11299/104285University of Minnesota. M.S. thesis. February 2011. Major: Stem cell biology. Advisor: Cindy Martin. 1 computer file (PDF); iv, 31 pages.Stem and progenitor cell populations occupy a specialized niche and are consequently exposed to hypoxic and oxidative stresses. We have previously established that the multidrug resistance protein Abcg2 is the molecular determinant of the side population (SP) progenitor cell population. There is an increase in Abcg2 expression, as well as increase in SP cell number, following injury. Transcriptome analysis of the SP cells isolated from the injured adult murine heart reveals enhanced expression of cytoprotective transcripts. We have previously demonstrated that hypoxia-inducible factor 2α (HIF-2α) binds an evolutionary conserved HIF-2 response element (HRE) in the murine Abcg2 promoter and activates Abcg2 expression. Overexpression of Abcg2 results in an increased ability to consume hydrogen peroxide. Importantly, overexpression of Abcg2 also conferred a cell survival benefit following exposure to hydrogen peroxide. In this study we have demonstrated that cytoprotection is dependent upon Abcg2 functioning as an active transporter. In-vitro analysis revealed SP cells proliferate in a delayed-onset manner, and such proliferation was affected by exposure to oxidative stress. Cytoprotective ‘priming’ also served to increase SP cell long-term viability. These results indicate that Abcg2 has a critical role in cytoprotection and Abcg2-expressing cells have important potential as progenitors in the adult.en-USStem cell biologyThesis or Dissertation