Pituitary progenitor cells tracked down by side population dissection

Stem Cells. 2009 May;27(5):1182-95. doi: 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" (Sca1(high)) but the remainder non-Sca1(high) fraction clusters the pituitary progenitor cells. Transcriptomal interrogation revealed in the non-Sca1(high) SP upregulated expression of the pituitary stem/progenitor cell markers Sox2 and Sox9, and of multiple factors critically involved in pituitary embryogenesis. The non-Sca1(high) SP encloses the cells that generate spheres and display multipotent hormone differentiation capacity. In culture conditions selecting for the non-Sca1(high) 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-Sca1(high) 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-Sca1(high) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ataxin-1
  • Ataxins
  • Cell Aggregation / drug effects
  • Cell Differentiation / drug effects
  • Cell Separation / methods*
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Embryonic Development / drug effects
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Female
  • Gene Expression Profiling
  • Genome / genetics
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Mice
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / drug effects
  • Multipotent Stem Cells / metabolism
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Phenotype
  • Pituitary Gland / cytology*
  • Pituitary Gland / drug effects
  • Pituitary Gland / embryology
  • Pituitary Gland, Anterior / cytology
  • SOXB1 Transcription Factors / metabolism
  • Stem Cell Niche / cytology
  • Stem Cell Niche / drug effects
  • Stem Cell Niche / metabolism
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Up-Regulation / drug effects

Substances

  • Ataxin-1
  • Ataxins
  • Atxn1 protein, mouse
  • Culture Media, Serum-Free
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse