Significance
Sonic hedgehog (SHH) signaling regulates adult stem cells in many self-renewing organs. However, whether SHH also regulates adult stem cells in tissues like the prostate is unclear. Improving therapy for prostate diseases, including benign prostatic hyperplasia and prostate cancer, will require a better understanding of the key signaling pathways that regulate prostate homeostasis and regeneration. We show that SHH signals from basal epithelial cells to the surrounding stroma in the adult prostate. Moreover, SHH responding cells repopulate the stroma and exhibit long-term self-renewal capacity during multiple rounds of involution and regeneration. Furthermore, we identified four stromal subtypes and present evidence for a model in which the three ductal stromal subtypes are maintained largely by distinct unipotent stem/progenitor cells.
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