RT Journal Article
T1 A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary
A1 García Lavandeira, Montserrat
A1 Quereda, Víctor
A1 Flores, Ignacio
A1 Saez, Carmen
A1 Díaz Rodríguez, Esther
A1 Japón, Miguel A.
A1 Ryan, Aymee K.
A1 Blasco, Maria A.
A1 Diéguez González, Carlos
A1 Malumbres, Marcos
A1 Álvarez Villamarín, María Clara
AB Background: The adult endocrine pituitary is known to host several hormone-producing cells regulating majorphysiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not muchis 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.Principal Findings: We have identified in rodents and humans a niche of non-endocrine cells characterized by theexpression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an orientedmanner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitaryspecific 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 orneurons 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.Significance: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by theexpression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to producedifferent 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 bythe lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion ofthe pituitary gland throughout life as well as protection from pituitary disease
PB PLOS
YR 2009
FD 2009
LK http://hdl.handle.net/10347/22886
UL http://hdl.handle.net/10347/22886
LA eng
NO Garcia-Lavandeira M, Quereda V, Flores I, Saez C, Diaz-Rodriguez E, Japon MA, et al. (2009) A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary. PLoS ONE 4(3): e4815. https://doi.org/10.1371/journal.pone.0004815
NO V.Q. was supported by a fellowship from the Spanish Ministry of Education and Science. This work was funded by grants from the Foundation of theAsociacion Espanola contra el Cancer (AECC; to M.M.), Foundation Mutua Madrilena Automovilista (to M.M.), Xunta de Galicia PGIDIT05BTF20803PR (to C.V.A. andC.D.) and the Ministry of Education and Science (MICINN; SAF2004-03131 and BFU2007-60571 to C.V.A. and SAF2006-05186, to M.M.). The Cell Division and CancerGroup of the CNIO is supported by the OncoCycle programme from the Comunidad de Madrid (S-BIO-0283-2006) and the Consolider-Ingenio (CSD2007-00017)program from the MICINN
DS Minerva
RD 28 abr 2026