SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland

*Division of Molecular Neuroendocrinology and
^§Division of Stem Cell Biology and Developmental Genetics, Medical Research Council, National Institute of Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom; and
^¶Developmental Endocrine Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, London WC1N 1EH, United Kingdom

Edited by Jacques Drouin, Institut de Recherches Cliniques de Montréal, Montreal, QC, Canada, and accepted by the Editorial Board December 19, 2007 (received for review August 21, 2007)

Abstract

The pituitary gland adapts the proportion of each of its endocrine cell types to meet differing hormonal demands throughout life. There is circumstantial evidence that multipotent adult progenitor cells contribute to this plasticity, but these cells have not been identified. Here, we describe a small (<0.05%) population of progenitor cells in the adult pituitary gland. We show that these cells express SOX2, a marker of several early embryonic progenitor and stem cell types, and form “pituispheres” in culture, which can grow, form secondary spheres, and differentiate to all of the pituitary endocrine cell types, as well as folliculostellate cells. Differentiation of cells in the pituispheres was associated with the expression of nestin, SOX9, and S100. Cells expressing SOX2 and E-cadherin are found throughout Rathke's pouch (RP) in embryos but persist in the adult gland, mostly in a narrow zone lining the pituitary cleft, but also are scattered throughout the pituitary. However, unlike in embryonic RP, most of these SOX2⁺ cells in the adult gland also express SOX9 and S100. We suggest that this SOX2⁺/SOX9⁺ population represents transit-amplifying cells, whereas the SOX2⁺/SOX9⁻ cells we identify are multipotent progenitor/stem cells persisting in the adult pituitary.

Footnotes

^‡To whom correspondence may be addressed. E-mail: irobins{at}nimr.mrc.ac.uk or teddy.fauquier{at}ens-lyon.fr
Author contributions: T.F., K.R., M.D., R.L.-B., and I.C.A.F.R. designed research; T.F. and K.R. performed research; T.F. and K.R. analyzed data; and T.F., K.R., R.L.-B., and I.C.A.F.R. wrote the paper.
↵ ^†Present address: Institut de Génomique Fonctionnelle, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. J.D. is a guest editor invited by the Editorial Board.
This article contains supporting information online at www.pnas.org/cgi/content/full/0707886105/DC1.