REGULATION OF STEM CELL FUNCTION IN THE ADULT BODY
- Author(s): Peiris, Tanuja Harshani
- Advisor(s): Oviedo, Nestor J
- et al.
Stem cells (SCs) distributed along the body have the capability to divide upon physiological demand and further differentiate into specialized cells that repair injured tissues. Thus, understanding regulatory mechanisms that control SC behavior during tissue repair and physiological demand is crucial for biomedical applications. Here we perform analysis of SCs in vivo, during tissue regeneration and physiological cellular turnover by using the planarian flatworm, Schmidtea mediterranea. Planarians provide an excellent model to explore fundamental aspects of cell regulation in their natural environment during adult tissue maintenance, regeneration and repair. In particular, I analyze components of (1) the TOR (Target of Rapamycin) and AKT pathway: an evolutionary conserved signaling system that has been implicated in cell cycle progression, metabolism, protein synthesis and cell growth. (2) DNA repair mechanisms. I have identified homologs for members of these pathways and designed a strategies to study their function with RNA interference (RNAi). Obtained results indicate that the TOR and AKT signaling is involved with controlling systemic SC behavior and can participate in physiological cell turnover but are unable to form regenerative blastema upon damage. Uniquely, TOR-independent SCs are capable of repairing damage by remodeling pre-existing tissue, which does not require active cell proliferation. Regional differences in cellular proliferation, migration and tissue repair exist along the anteroposterior (AP) axis in vertebrate and invertebrate animals. Despite years of research, the basic mechanisms controlling cell division and tissue repair along the body remain poorly understood. Loss-of-function genetic approaches allowed to identify mechanisms controlling regional differences in cell proliferation along the planarian AP axis. These results suggest interplay between DNA repair mechanisms and tumor suppressor genes as capable of regulating cell behavior in specific areas of the adult body. Here I explored the possibility of controlling tissue regeneration and repair by exploring interactions between DNA double-strand break repair mechanisms through Rad51, and the tumor suppressors p53 and the retinoblastoma pathways. We hope to expand these results to understand stem cell-directed regeneration of particular tissues to enable the implementation of effective biomedical approaches.