A GRFa2/Prop1/stem (GPS) cell niche in the pituitary

The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation dur...

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Veröffentlicht in:PloS one 2009-03, Vol.4 (3), p.e4815
Hauptverfasser: Garcia-Lavandeira, Montse, Quereda, Víctor, Flores, Ignacio, Saez, Carmen, Diaz-Rodriguez, Esther, Japon, Miguel A, Ryan, Aymee K, Blasco, Maria A, Dieguez, Carlos, Malumbres, Marcos, Alvarez, Clara V
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creator Garcia-Lavandeira, Montse
Quereda, Víctor
Flores, Ignacio
Saez, Carmen
Diaz-Rodriguez, Esther
Japon, Miguel A
Ryan, Aymee K
Blasco, Maria A
Dieguez, Carlos
Malumbres, Marcos
Alvarez, Clara V
description The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as protection from pituitary disease.
doi_str_mv 10.1371/journal.pone.0004815
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In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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L.</contributor><creatorcontrib>Garcia-Lavandeira, Montse</creatorcontrib><creatorcontrib>Quereda, Víctor</creatorcontrib><creatorcontrib>Flores, Ignacio</creatorcontrib><creatorcontrib>Saez, Carmen</creatorcontrib><creatorcontrib>Diaz-Rodriguez, Esther</creatorcontrib><creatorcontrib>Japon, Miguel A</creatorcontrib><creatorcontrib>Ryan, Aymee K</creatorcontrib><creatorcontrib>Blasco, Maria A</creatorcontrib><creatorcontrib>Dieguez, Carlos</creatorcontrib><creatorcontrib>Malumbres, Marcos</creatorcontrib><creatorcontrib>Alvarez, Clara V</creatorcontrib><title>A GRFa2/Prop1/stem (GPS) cell niche in the pituitary</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. 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metabolism</topic><topic>Pathology</topic><topic>Physiological aspects</topic><topic>Physiology</topic><topic>Pituitary</topic><topic>Pituitary gland</topic><topic>Pituitary Gland - cytology</topic><topic>Pituitary Gland - metabolism</topic><topic>Pituitary Hormones - metabolism</topic><topic>Polarity</topic><topic>Pregnancy</topic><topic>Prophet of pit-1 protein</topic><topic>Puberty</topic><topic>Rats</topic><topic>Relative abundance</topic><topic>Rodents</topic><topic>Sox9 protein</topic><topic>Spheroids</topic><topic>Stage-Specific Embryonic Antigens - metabolism</topic><topic>Stem Cell Niche - metabolism</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - metabolism</topic><topic>Telomerase</topic><topic>Telomere - ultrastructure</topic><topic>Telomeres</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Vimentin</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Garcia-Lavandeira, Montse</creatorcontrib><creatorcontrib>Quereda, Víctor</creatorcontrib><creatorcontrib>Flores, Ignacio</creatorcontrib><creatorcontrib>Saez, Carmen</creatorcontrib><creatorcontrib>Diaz-Rodriguez, Esther</creatorcontrib><creatorcontrib>Japon, Miguel A</creatorcontrib><creatorcontrib>Ryan, Aymee K</creatorcontrib><creatorcontrib>Blasco, Maria A</creatorcontrib><creatorcontrib>Dieguez, Carlos</creatorcontrib><creatorcontrib>Malumbres, Marcos</creatorcontrib><creatorcontrib>Alvarez, Clara V</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - 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L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A GRFa2/Prop1/stem (GPS) cell niche in the pituitary</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-03-13</date><risdate>2009</risdate><volume>4</volume><issue>3</issue><spage>e4815</spage><pages>e4815-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as protection from pituitary disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19283075</pmid><doi>10.1371/journal.pone.0004815</doi><oa>free_for_read</oa></addata></record>
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subjects Abundance
Animals
Biomarkers
Bromodeoxyuridine - pharmacology
Cell Biology/Morphogenesis and Cell Biology
Cell Biology/Neuronal Signaling Mechanisms
Cell culture
Cell cycle
Cell division
Cell Proliferation
Cyclin-dependent kinase 4
Cyclin-dependent kinases
Diabetes and Endocrinology/Neuroendocrinology and Pituitary
E-cadherin
Elongation
Gene Expression
Genes
Glial Cell Line-Derived Neurotrophic Factor Receptors - genetics
Glial Cell Line-Derived Neurotrophic Factor Receptors - metabolism
Global Positioning System
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Homeostasis
Hormones
Humans
Hypopituitarism
Hypopituitarism - metabolism
Intermediate filament proteins
Kinases
Lymphocytes B
Medicine
Mice
Nervous system
Neuroectoderm
Nuclei (cytology)
Oct-4 protein
Octamer Transcription Factor-3 - metabolism
Pathology
Physiological aspects
Physiology
Pituitary
Pituitary gland
Pituitary Gland - cytology
Pituitary Gland - metabolism
Pituitary Hormones - metabolism
Polarity
Pregnancy
Prophet of pit-1 protein
Puberty
Rats
Relative abundance
Rodents
Sox9 protein
Spheroids
Stage-Specific Embryonic Antigens - metabolism
Stem Cell Niche - metabolism
Stem cell transplantation
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Telomerase
Telomere - ultrastructure
Telomeres
Transcription Factors - genetics
Transcription Factors - metabolism
Tumorigenesis
Tumors
Vimentin
β-Catenin
title A GRFa2/Prop1/stem (GPS) cell niche in the pituitary
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