Abstract
Organ development, regeneration and cancer initiation are typically influenced by the proliferation and lineage plasticity of tissue-specific stem cells. Prostate intermediate cells, which exhibit characteristics of both basal and luminal cells, are prevalent in pathological states and during organ development. However, the identity, fate and function of these intermediate cells in prostate development are not well understood. Through single-cell RNA-seq analysis on neonatal urogenital sinus tissue, we identified intermediate cells exhibiting stem cell potential. A notable decline in the population of intermediate cells was observed during prostate development. Prostate intermediate cells were specifically labeled in early and late postnatal development by the enhanced dual-recombinase-mediated genetic tracing systems. Our findings revealed that these cells possess significant stem cell capabilities as demonstrated in organoid formation and cell fate mapping assays. These intermediate cells also exhibited intrinsic bipotential properties, enabling them to differentiate into both basal and luminal cells. Additionally, we discovered a novel transition from intermediate cell expressing neuroendocrine markers to neuroendocrine cell during prostate development. This study highlights intermediate cells as a crucial stem cell population and enhances our understanding of their role in prostate development and the plasticity of prostate cancer lineage.