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.
University of Minnesota. M.S. thesis. February 2011. Major: Stem cell biology. Advisor: Cindy Martin. 1 computer file (PDF); iv, 31 pages.
Maher, Travis Joseph.
Side population cells possess a stem cell nature: cytoprotection, proliferation, and role of functional recovery in the murine heart..
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