Adult stem cells are fundamental to tissue resilience, allowing organisms to restore function after injury or environmental stress. Planarians, with their remarkable regenerative abilities, serve as an ideal model for studying how adult stem cells integrate environmental and molecular signals to maintain tissue homeostasis. This dissertation investigates the mechanisms that enable planarian stem cells to preserve genomic integrity and orchestrate regeneration. First, we demonstrate that Ataxia-Telangiectasia Mutated (ATM) kinase is the main driver for radiation-induced apoptosis. Knockdown of ATM allows planarian stem cells to survive otherwise lethal ionizing radiation and enables long-term survival and regeneration. Second, we identify a novel Slit-independent RoboA signaling pathway that restricts stem cell plasticity, functioning in concert with Anosmin-1 and FoxA to enforce fidelity of brain regeneration. Together, these studies reveal how planarian adult stem cells balance plasticity, genomic stability, and environmental inputs to ensure robust regeneration, providing new insights into fundamental principles of stem cell biology.