Pituitary progenitor cells tracked down by side population dissection
Faculty of Medicine and Health Sciences
Stem cells. - Dayton, Ohio, 1993, currens
, p. 1182-1195
University of Antwerp
The pituitary gland represents the endocrine core, governing the body's hormonal landscape by adapting its cellular composition to changing demands. It is assumed that stem/progenitor cells are involved in this remodeling. Recently, we uncovered a candidate stem/progenitor cell population in the anterior pituitary. Here, we scrutinized this "side population" (SP) and show that, unexpectedly, not the subset expressing high levels of "stem cell antigen-1" (Sca1high) but the remainder non-Sca1high fraction clusters the pituitary progenitor cells. Transcriptomal interrogation revealed in the non-Sca1high SP upregulated expression of the pituitary stem/progenitor cell markers Sox2 and Sox9, and of multiple factors critically involved in pituitary embryogenesis. The non-Sca1high SP encloses the cells that generate spheres and display multipotent hormone differentiation capacity. In culture conditions selecting for the non-Sca1high subset within the SP, stem cell growth factors that induce SP expansion, affect transcription of embryonic factors, suggesting impact on a developmental program that unfolds within this SP compartment. Non-Sca1high SP cells, revealed by Sox2 expression, are observed in the postulated periluminal stem/progenitor cell niche, but also in small groups scattered over the gland, thereby advocating the existence of multiple niches. In early postnatal mice undergoing a pituitary growth wave, Sox2+ cells are more abundant than in adults, concordant with a larger SP and higher non-Sca1high proportion. Together, we tracked down pituitary progenitor cells by SP phenotype, and thus provide a straightforward method to isolate and scrutinize these cells from the plastic pituitary ex vivo, as well as a culture system for in-depth exploration of their regulatory network.