Pituitary Progenitor Cells Tracked Down by Side Population Dissection
Open Access
- 26 February 2009
- journal article
- tissue specific-stem-cells
- Published by Oxford University Press (OUP) in The International Journal of Cell Cloning
- Vol. 27 (5), 1182-1195
- https://doi.org/10.1002/stem.51
Abstract
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. Stem Cells 2009;27:1182–1195Keywords
This publication has 57 references indexed in Scilit:
- A Novel Dominant Negative Mutation of OTX2 Associated with Combined Pituitary Hormone DeficiencyJournal of Clinical Endocrinology & Metabolism, 2008
- Genetic approaches identify adult pituitary stem cellsProceedings of the National Academy of Sciences of the United States of America, 2008
- SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary glandProceedings of the National Academy of Sciences of the United States of America, 2008
- Identification of stem cells in small intestine and colon by marker gene Lgr5Nature, 2007
- Side Population Cells in the Mouse Thyroid Exhibit Stem/Progenitor Cell-Like CharacteristicsEndocrinology, 2007
- Hes1 is required for pituitary growth and melanotrope specificationDevelopmental Biology, 2007
- SOX9 is required for maintenance of the pancreatic progenitor cell poolProceedings of the National Academy of Sciences of the United States of America, 2007
- Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesisGenes & Development, 2006
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006
- Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.The Journal of Experimental Medicine, 1996