UC San Diego

Adult stem cells reside in specialized microenvironments, or niches, that have an important role in regulating stem cell behavior. Therefore, tight control of niche number, size, and function is necessary to ensure the proper balance between stem cells and progenitor cells available for tissue homeostasis and wound repair. Identification of genetic networks that regulate stem cell niches are of particular interest for their potential roles in regenerative medicine. This dissertation work utilizes the Drosophila testis as a model for understanding how genetic factors regulate stem cell niche maintenance and regeneration. In Drosophila males, the germline stem cell niche is located at the tip of the testis where germline and somatic cyst stem cells surround the apical hub, a cluster of approximately 10-15 somatic cells that are required for stem cell self-renewal. Findings described in Chapter 2 led to the hypothesis that somatic cyst stem cells contribute to the apical hub and identified an important role for the Snail family transcription factor escargot within the stem cell niche. This work also identified adhesion to the hub is required for both germline and somatic cyst stem cell maintenance. Work presented in Chapter 3 demonstrates the cell type specific requirements of escargot within hub cells (maintenance) and somatic cyst stem cells (maintenance and regulation of proliferation). In addition, Chapter 3 provides direct evidence that the hub is absolutely required for germline and somatic cyst stem cell maintenance. Using both genetic and genomic approaches, we demonstrate that an interaction between escargot and the transcripton factor Stat92E coordinately act in regulating hub cell maintenance and somatic cyst stem cell activity. These data build the framework for findings described in Chapter 4 that provide preliminary evidence that the AP-4 transcription factor cropped, a putative transcriptional target of escargot, is required for hub maintenance. Futhermore, these data suggest that the hub is capable of regeneration during adulthood. This dissertation highlights the dynamic relationship between stem cells and niche support cells and provides insight into genetic programs that regulate niche size and function to support normal tissue homeostasis and organ regeneration during development and adulthood.