Adult stem cells act as a reservoir for the regeneration of damaged tissue. These stem cells normally reside in a quiescent state in order to minimize unnecessary replication to presumably prolong their life-span, and they undergo ‘self-renewal’ (e.g., a specific type of cellular proliferation, maintaining ‘stemness’) only when damaged tissue needs to be regenerated (77). In this circumstance, stem cells are transiently stimulated to undergo asymmetric self-renewal, which generates one identical stem cell and one progenitor cell. The generation of the identical stem cells is critical for maintaining the stem cell pool, whereas the new progenitor cells proliferate (hence their name ‘transient amplifying (TA) cells’) and differentiate to replace the damaged tissue (78) (Figure 5A). Maintaining a balance between sufficient numbers of progenitor cells and stem cells is critical for individual homeostasis (e.g., aging or cancer) (Figure 5). For example, recent studies have revealed that the reduced proliferative potential of stem cells and the subsequent depletion of the stem cell pool are correlated with age-related diseases such as rheumatoid arthritis, osteoarthritis, refractory hypertension (78, 79). More clearly, an animal model
