The adult pituitary contains a cell population displaying stem/progenitor cell and early embryonic characteristics.
A side population (SP) has been identified in a number of tissues, where it typically represents a small population enriched in stem/progenitor cells. In this study we show that the adult mouse anterior pituitary (AP) also contains a characteristic SP displaying verapamil-sensitive Hoechst dye efflux capacity. A majority of the SP cells express stem cell antigen 1 at a high level (Sca1high). Using (semi)quantitative RT-PCR and immunofluorescence, we characterized the Sca1high SP as a population enriched in cells expressing stem/progenitor cell-associated factors and components of the Notch, Wnt, and sonic hedgehog signaling pathways, functional in stem cell homeostasis as well as in early pituitary embryogenesis. Lhx4, a transcription factor pivotal for early embryonic development of the AP, was only detected in the Sca1high SP, whereas Lhx3, in contrast to Lhx4 not down-regulated after AP development, was only found in the main population. The Sca1high SP was depleted from cells expressing phenotypic markers of differentiated AP cells (hormones), but contained a small proportion of folliculo-stellate cells. Stem cells of many tissues can clonally expand to nonadherent spheres in culture. Clonal spheres also developed in AP cell cultures. Spheres showed an expression pattern resembling that of Sca1high SP cells. Moreover, the sphere-initiating cells of the pituitary segregated to the SP and not to the main population. In conclusion, we show that the adult pituitary contains a hitherto undescribed population of cells with SP phenotype and clonal expansion capacity. These cells express (signaling) molecules generally found in stem/progenitor cells and/or operative during pituitary early embryonic development. These characteristics are supportive of a stem/progenitor cell phenotype.
Chen
Jianghai
J
Laboratory of Cell Pharmacology, Department of Molecular Cell Biology, University of Leuven (K.U.Leuven) School of Medicine, Campus Gasthuisberg (O&N), Herestraat 49, B-3000 Leuven, Belgium.
Hersmus
Nicole
N
Van Duppen
Vik
V
Caesens
Pieter
P
Denef
Carl
C
Vankelecom
Hugo
H
D000367:Age Factors; D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics; D000067696:Ataxin-1; D000067528:Ataxins; D015415:Biomarkers; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D060850:LIM-Homeodomain Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000196:embryology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D051880:Receptors, Notch; D013234:Stem Cells / Q000166:cytology*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D051153:Wnt Proteins
D018952:Antigens, CD34; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D015415:Biomarkers; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; C108538:Lhx4 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051880:Receptors, Notch; C465570:Shh protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D019009:Proto-Oncogene Proteins c-kit