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Characterization of germline stem cell behavior during aging in Drosophila melanogaster


Adult stem cells replenish tissues during normal cellular turnover or injury. A stem cell divides asymmetrically to produce one stem cell (a process called self-renewal), and one daughter cell that initiates differentiation. The mechanisms ensuring the balance of cells are critical for tissue homeostasis. Misregulation of stem cells during disease or aging can lead to impaired tissue maintenance and repair resulting in diminished life quality or death of an individual. Stem cells are located in a microenvironment, or niche, within a tissue. The niche, composed of other cells, ECM, and/or a basement membrane, provides extrinsic cues to stem cells that regulate self- renewal, maintenance, and survival. Therefore, analyses of stem cells should include the niche, to ensure that an observation is physiologically relevant. While in vivo studies of stem cells are critical, complex vertebrate tissues are difficult for 1) identifying stem cells 2) determining niche components 3) deciphering signaling pathways within stem cells, and between stem cells and the niche. Therefore, studies of stem cells within the context of disease or aging would add more hurdles to the research process. This dissertation presents research using the powerful model organism, Drosophila melanogaster, to study the effects of aging on germline stem cell (GSC) behavior in the testis, a well-characterized tissue. Chapter 2 shows that aging results in reduced GSC function due to extrinsic changes to the niche and intrinsic changes to the GSCs. Janus kinase -Signal Transducer and Activator of Transcription, Jak-STAT, signaling that regulates stem cell maintenance, was reduced during aging, and restoration of signaling led to a rescue of GSC number within the niche in aged animals. Male flies are able to replace lost GSCs through reversion (dedifferentiation) of early germline progenitor cells. Chapter 3 shows that GSC numbers are lower during aging possibly due to compromised reversion. Analysis of early cyst cells, one of the components of the niche, shows defects in response to reversion in aged flies. This dissertation summarizes that interactions between the stem cells and their niche dictate tissue health; changes to the niche and stem cells lead to decreased tissue homeostasis during aging

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