Electronic Thesis/Dissertation


Function and Characterization of a Mouse Mammary Gland Stem Cell Microenvironment Open Access

The concept of a stem cell microenvironment has been well studied and documented. The ability of the mammary gland to maintain stem cell activity throughout the lifetime of the animal despite aging and repeated expansion and depletion of the mammary epithelium through rounds of pregnancy, lactation, and involution provides evidence for the presence of stem cell microenvironments in the mouse mammary gland. Understanding how these microenvironments function and what their capacity and limitations are can provide invaluable information on their ability to maintain and control stem cell behavior. Elucidating the complex interactions between the mammary gland microenvironment and stem cells will also provide us with a greater understanding of mammary tissue development and tumorigenesis. The following series of experiments were designed to answer questions regarding the capacity, function, characterization, and power of a mammary microenvironment. Our results indicate that the mammary microenvironment has the capacity to reprogram stem/progenitor cells from all three germ layers, and to reprogram uncommitted bona fide embryonic stem cells. We have also determined a couple critical niche components, the presence of ER-alpha; and the need for live actively dividing cells. Lastly, we have discovered that signals from incompetent mammary niches cannot reprogram alternate stem/progenitor cells, and based on a study of these deficient populations, identified several genes of interest that will help further define and characterize the mammary microenvironment. The data we have obtained about how the microenvironment directs cell behavior provides important clues towards understanding stem cell control and its potential use in breast cancer therapy.

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