Fig. 4
From: Forkhead box O proteins: steering the course of stem cell fate
Evolutionary role of FOXOs in the regulation of stem cell fate. In organisms with abundant pluripotent stem cells like cnidarians and acoels, FOXOs promote stem cell self-renewal, enabling rapid regeneration of body parts after injury. This strategy is also observed in mammalian embryonic stem cells (ESCs). However, FOXOs in adult mammals primarily regulate quiescence in species with limited adult stem cells (ASCs), preserving the stem cell pool and minimizing depletion or inappropriate cell growth. FOXOs also play a role in stem cell differentiation, either promoting or inhibiting it as needed for tissue homeostasis. This functional divergence of FOXO genes allows organisms to balance tissue maintenance and long-term preservation of the stem cell pool