Symmetrical and asymmetrical division analysis provides evidence for a hierarchy of prostate epithelial cell lineages

Abstract

Although symmetrical and asymmetrical divisions of stem cells have been extensively studied in invertebrate and mammalian neural epithelia, their role remains largely unknown in mammalian non-neural epithelial development, regeneration and tumorigenesis. Here, using basal and luminal cell-specific markers and cell lineage tracing transgenic mice, we report that in developing prostatic epithelia, basal and luminal cells exhibit distinct division modes. While basal cells display both symmetric and asymmetric divisions leading to different cell fates, luminal cells only exhibit symmetrical divisions. Examination of cell division modes in prostate-specific Pten-null mice indicates that both luminal and basal cells can be cellular origins for prostate cancer. Furthermore, analysis of Sox2-expressing cells in p63 and Pten-null mice suggests that basal cells contribute to the luminal population and tumorigenesis. These findings provide direct evidence for the existence of a hierarchy of epithelial cell lineages during prostate development, regeneration and tumorigenesis.

Quantitative lineage tracing strategies to resolve multipotency in tissue-specific stem cells

“…In this study, we initiated the tracing in the prostate at a different time point than in the MG to assess the fate of BCs during prostate postnatal development (which has been previously described) Table S6 for further information on statistics. (Ousset et al 2012;Pignon et al 2013;Wang et al 2014). If we had performed the tracing in the prostate at the same time point as in the MG, when the postnatal development of the prostate is largely completed, we would have assessed the fate of the unipotent SCs that sustain prostate adult homeostasis (Wang et al , 2013(Wang et al , 2014Liu et al 2011;Choi et al 2012;Ousset et al 2012;Lu et al 2013;Pignon et al 2013).…”

“…Lineage tracing experiments during prostate postnatal development, adult homeostasis, and adult regeneration after castration suggested that prostate postnatal development is mediated by multipotent and unipotent SCs, whereas adult prostate maintenance and regeneration are mediated by basal and luminal unipotent SCs (Wang et al , 2013(Wang et al , 2014Liu et al 2011;Choi et al 2012;Ousset et al 2012;Lu et al 2013;Pignon et al 2013).…”

“…To challenge our biostatistical analysis of multipotency, we performed multicolor mosaic tracing during prostate postnatal development, during which multipotent SCs have been suggested to contribute to morphogenesis (Ousset et al 2012;Pignon et al 2013;Wang et al 2014). K5CreER T2 /Rosa-Confetti newborn mice (postnatal day 1 [P1]) were induced with a single low dose of TAM (0.1 mg) and analyzed 10 d later (Fig.…”

Prostate Sphere-forming Stem Cells Are Derived from the P63-expressing Basal Compartment

“…In addition, both luminal and basal compartments contain singlelineage P-SCs that only give rise to daughter cells in their respective compartments (7,8). Interestingly, the basal cells display both symmetrical and asymmetrical divisions, whereas luminal cells only exhibit symmetrical divisions (9). Asymmetrical divisions of stem cells reflect their capacity to self-renew and produce daughter cells for differentiated progeny.…”

Cancer Stem Cells

“…(continued) Wang et al 2014). Later, Rios et al highlighting the potential caveats of these approaches identified a single bipotent stem cell in the mammary gland (Rios et al 2014).…”