Daniel Yi, Michael Kahn
Somatic stem cells, as well as cancer stem cells, exist in two basic "states", quiescent versus activated. The regulation of the balance between quiescence and activation is critical to tissue homeostasis and repair after injury. Additionally, after being activated, the decision to divide symmetrically or asymmetrically is critical. Aberrant regulation of stem cell quiescence and mode of mitotic division is associated with aging and diseases of aging including cancer, fibrosis, sarcopenia and neurodegeneration. Based on over 25 years of chemical genetic and genetic investigation, we discuss the differential roles of the two Kat3 coactivators (Kat3A/CREBBP/CBP and Kat3B/EP300/p300) in regulating stem cell quiescence and the mode of division of activated stem cells. The ability to pharmacologically regulate differential Kat3 coactivator usage has important implications to ameliorate the aging process as well as to eliminate quiescent cancer stem cells, which are the cause of disease relapse and metastasis.