Genetic approaches identify adult pituitary stem cells

Abstract

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.

Programmed cell senescence: role of IL-6 in the pituitary

“…The recent characterization of pituitary stem cells (Fauquier et al 2008, Garcia-Lavandeira et al 2009, 2015, Vankelecom & Gremeaux 2010 implies the possibility of defining their mechanisms involved not only in pituitary cell renewal but also in pituitary tumorigenesis. Several groups have described the presence within the pituitary tumor of a side population containing cells with high efflux capacity and enriched with potentially tumor stem cells (Gleiberman et al 2008, Florio 2011, Mertens et al 2015. In line with that, enhanced selfrenewal as a mechanism of tumor initiation has been reported in pituitary adenomas (Hosoyama et al 2010, Gaston-Massuet et al 2011, Andoniadou et al 2013, Donangelo et al 2014.…”

The role of proto-oncogene GLI1 in pituitary adenoma formation and cell survival regulation

“…Sox2C cells in the mouse pituitary can self-renew and are multipotent, giving rise to any of the endocrine cell types of the gland (Gleiberman et al 2008). Only recently, Sox2C cells were shown to contribute to pituitary tumor formation through paracrine signaling (Andoniadou et al 2013).…”

Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism

“…To unravel the functional role of JNK1 in the CNS and pituitary, we generated mice with targeted ablation of JNK1. It has recently been demonstrated that in addition to neurons, the Nestin gene is also expressed in pituitary stem cells, allowing deletion of target genes in all cell types of the adult pituitary using Nestin-Cre transgenic mice (25). Hence, after generation of mice with a loxP-flanked JNK1 allele (Fig.…”