Sox2+ Stem/Progenitor Cells in the Adult Mouse Pituitary Support Organ Homeostasis and Have Tumor-Inducing Potential

SummarySox2+ adult mouse pituitary cells can self-renew and terminally differentiate in vitro, but their physiological role in vivo and possible contribution to oncogenesis remain largely unknown. Using genetic lineage tracing, we show here that the Sox2+ cell compartment of both the embryonic and adult pituitary contains stem/progenitor cells that are able to differentiate into all hormone-producing lineages and contribute to organ homeostasis during postnatal life. In addition, we show that targeted expression of oncogenic β-catenin in Sox2+ cells gives rise to pituitary tumors, but, unexpectedly, the tumor mass is not derived from the Sox2+ mutation-sustaining cells, suggesting a paracrine role of Sox2+ cells in pituitary oncogenesis. Our data therefore provide in vivo evidence of a role for Sox2+ stem/progenitor cells in long-term physiological maintenance of the adult pituitary, and highlight an unexpected non-cell-autonomous role for these cells in the induction of pituitary tumors.Video Abstrac