During tissue homeostasis, normal stem cells self-renew and repopulate the diverse cell types found within the tissue via a series of carefully controlled symmetric and asymmetric cell divisions (ACDs). The notion that solid tumors comprise a subset of cancer stem cells (CSCs) with dysregulated self-renewal and excessive symmetric cell divisions has led to numerous studies aimed to elucidate the mechanisms regulating ACD under steady-state conditions, during stem-cell expansion and in cancer. In this perspective, we focus on a type of asymmetry that can be established during ACD, called non-random co-segregation of template DNA, which has been identified across numerous species, cell types, and cancers. We discuss the role of p53 loss in maintaining self-renewal in both normal and malignant cells. We then review our current knowledge of the mechanisms underlying co-segregation of template DNA strands and the stem-cell pathways associated with it in normal and CSCs.
Keywords: Notch; Wnt; asymmetric cell division; cancer stem cells; co-segregation of template DNA; immortal DNA; p53.