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BIOLOGICAL SCIENCES / DEVELOPMENTAL BIOLOGY
Genetic approaches identify adult pituitary stem cells

Anatoli S. Gleiberman^*,, Tatyana Michurina, Juan M. Encinas, Jose L. Roig, Peter Krasnov, Francesca Balordi, Gord Fishell, Michael G. Rosenfeld^*,¶, and Grigori Enikolopov^,¶

*Howard Hughes Medical Institute, Department of Medicine, University of California at San Diego School of Medicine, La Jolla, CA 92093-0648; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724; and Smilow Neuroscience Program and Department of Cell Biology, New York University School of Medicine, New York, NY 10016

Contributed by Michael G. Rosenfeld, February 21, 2008 (received for review January 11, 2008)

Adult tissues undergo continuous cell turnover in response to stress, damage, or physiological demand. New differentiated cells are generated from dedicated or facultative stem cells or from self-renewing differentiated cells. Here we describe a different stem cell strategy for tissue maintenance, distinct from that observed for dedicated or facultative stem cells. We report the presence of nestin-expressing adult stem cells in the perilumenal region of the mature anterior pituitary and, using genetic inducible fate mapping, demonstrate that they serve to generate subsets of all six terminally differentiated endocrine cell types of the pituitary gland. These stem cells, while not playing a significant role in organogenesis, undergo postnatal expansion and start producing differentiated progeny, which colonize the organ that initially entirely consisted of differentiated cells derived from embryonic precursors. This generates a mosaic organ with two phenotypically similar subsets of endocrine cells that have different origins and different life histories. These parallel but distinct lineages of differentiated cells in the gland may help the maturing organism adapt to changes in the metabolic regulatory landscape.

anterior pituitary | Cre | Lhx3 | nestin | nestin-GFP

Author contributions: A.S.G., M.G.R., and G.E. designed research; A.S.G., T.M., J.M.E., J.L.R., P.K., and F.B. performed research; F.B., G.F., M.G.R., and G.E. contributed new reagents/analytic tools; A.S.G., T.M., J.M.E., J.L.R., F.B., G.F., M.G.R., and G.E. analyzed data; and A.S.G., M.G.R., and G.E. wrote the paper.

Present address: Cleveland Biolabs, Inc., Buffalo, NY 14203.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0801644105/DCSupplemental.

^¶To whom correspondence may be addressed. E-mail: mrosenfeld{at}ucsd.edu or enik{at}cshl.edu

© 2008 by The National Academy of Sciences of the USA

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PNAS 2008 105: 6209-6210. [Full Text]