The decision for a stem cell to undergo a symmetric versus an asymmetric differentiation is probably the most critical cellular decision process in adults, as it probably underlies a large array of diseases, is associated with a decrease in tissue maintenance/homeostasis and the ability to repair properly, may mediate pathological processes such as cancer, fibrosis and neurodegeneration, and may be the underlying problem associated in general with aging. Interestingly and importantly, the decision to divide asymmetrically or symmetrically may be the major fundamental intrinsic difference between normal somatic stem and cancer stem cells. Based upon work done primarily in our laboratory over the past 10 years (both published and unpublished data), the article provides perspective on the critical importance of symmetric versus asymmetric divisions and the role of differential usage of the highly homologous coactivators Creb-binding protein (CBP) or p300 in the Wnt/catenin signaling cascade in stem cells and how they can be pharmacologically manipulated.
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