Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential

Cynthia Lilian Andoniadou, Danielle Matsushima, Seyedeh Neda Mousavy Gharavy, Massimo Signore, Albert Ian Mackintosh, Marie Schaeffer, Carles Gaston-Massuet, Patrice Mollard, Thomas Stanley Jacques, Paul Le Tissier, Mehul Tulsidas Dattani, Larysa Halyna Pevny, Juan Pedro Martinez-Barbera

Research output: Contribution to journalArticlepeer-review

Abstract

Sox2(+) 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.

Original languageEnglish
Pages (from-to)433-45
Number of pages13
JournalCell Stem Cell
Volume13
Issue number4
DOIs
Publication statusPublished - 3 Oct 2013

Keywords

  • Animals
  • Cells, Cultured
  • Homeostasis
  • Mice
  • Mice, Transgenic
  • Mutation
  • Pituitary Gland
  • Pituitary Neoplasms
  • SOXB1 Transcription Factors
  • Stem Cells

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