Spatiotemporal regulation of multipotency during prostate development

Abstract

The prostate is formed by a branched glandular epithelium composed of basal cells (BCs) and luminal cells (LCs). Multipotent and unipotent stem cells (SCs) mediate the initial steps of prostate development whereas BCs and LCs are self-sustained in adult mice by unipotent lineage-restricted SCs. The spatiotemporal regulation of SC fate and the switch from multipotency to unipotency remain poorly characterised. Here, by combining lineage tracing, whole tissue imaging, clonal analysis and proliferation kinetics, we uncover the cellular dynamics that orchestrate prostate postnatal development. We found that at the early step of development, multipotent basal SCs are located throughout the epithelium, and are progressively restricted at the distal tip of the ducts, where together with their progeny set up the different branches and the final structure of prostate. In contrast, pubertal development is mediated by unipotent lineage-restricted SCs. Our results uncover the spatiotemporal regulation of the switch from multipotency to unipotency during prostate development.