Sox2(+) adult mouse pituitary cells can self-renew and terminally differentiate in vitro, but their physiological role in vivo and possible contribution to oncogenesis remain largely unknown. Using genetic lineage tracing, we show here that the Sox2(+) cell compartment of both the embryonic and adult pituitary contains stem/progenitor cells that are able to differentiate into all hormone-producing lineages and contribute to organ homeostasis during postnatal life. In addition, we show that targeted expression of oncogenic β-catenin in Sox2(+) cells gives rise to pituitary tumors, but, unexpectedly, the tumor mass is not derived from the Sox2(+) mutation-sustaining cells, suggesting a paracrine role of Sox2(+) cells in pituitary oncogenesis. Our data therefore provide in vivo evidence of a role for Sox2(+) stem/progenitor cells in long-term physiological maintenance of the adult pituitary, and highlight an unexpected non-cell-autonomous role for these cells in the induction of pituitary tumors.
Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1
Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway
Visualization of S100B-positive neurons and glia in the central nervous system of EGFP transgenic mice
SOX2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult
Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region
Nuclear beta-catenin accumulation as reliable marker for the differentiation between cystic craniopharyngiomas and rathke cleft cysts: a clinico-pathologic approach
Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain
SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland
Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model
Distinct developmental roles of cell cycle inhibitors p57Kip2 and p27Kip1 distinguish pituitary progenitor cell cycle exit from cell cycle reentry of differentiated cells
Lin-Sca-1+CD49fhigh stem/progenitors are tumor-initiating cells in the Pten-null prostate cancer model
Combinations of genetic mutations in the adult neural stem cell compartment determine brain tumour phenotypes
Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans
Significant quantitative and qualitative transition in pituitary stem / progenitor cells occurs during the postnatal development of the rat anterior pituitary
Activated phenotype of the pituitary stem/progenitor cell compartment during the early-postnatal maturation phase of the gland
Paracrine TGF-β signaling counterbalances BMP-mediated repression in hair follicle stem cell activation
Identification of novel pathways involved in the pathogenesis of human adamantinomatous craniopharyngioma.
The adult pituitary shows stem/progenitor cell activation in response to injury and is capable of regeneration
Developmental stage and time dictate the fate of Wnt/β-catenin-responsive stem cells in the mammary gland
Regenerative capacity of the adult pituitary: multiple mechanisms of lactotrope restoration after transgenic ablation
Pituitary cell differentiation from stem cells and other cells: toward restorative therapy for hypopituitarism?
Generation of CD44 gene-deficient mouse derived induced pluripotent stem cells: CD44 gene-deficient iPSCs
Adamantinomatous craniopharyngiomas express tumor stem cell markers in cells with activated Wnt signaling: further evidence for the existence of a tumor stem cell niche?
Concise Review: Paracrine Role of Stem Cells in Pituitary Tumors: A Focus on Adamantinomatous Craniopharyngioma
Histopathology and molecular characterisation of intrauterine-diagnosed congenital craniopharyngioma
Transcription factor 7-like 1 is involved in hypothalamo-pituitary axis development in mice and humans
Notch-Dependent Pituitary SOX2(+) Stem Cells Exhibit a Timed Functional Extinction in Regulation of the Postnatal Gland
The role of the sonic hedgehog signalling pathway in patients with midline defects and congenital hypopituitarism
Insights into the infiltrative behavior of adamantinomatous craniopharyngioma in a new xenotransplant mouse model
Expression and clinical relevance of paired box protein 7 and sex determining region Y-box 2 in canine corticotroph pituitary adenomas
Establishment of the neurogenic boundary of the mouse retina requires cooperation of SOX2 and WNT signaling
Localization of juxtacrine factor ephrin-B2 in pituitary stem/progenitor cell niches throughout life
Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland
Can the 'neuron theory' be complemented by a universal mechanism for generic neuronal differentiation
Imaging Invasion: Micro-CT imaging of adamantinomatous craniopharyngioma highlights cell type specific spatial relationships of tissue invasion
Isolation of adult pituitary stem/progenitor cell clusters located in the parenchyma of the rat anterior lobe
Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes
Regulation of pituitary stem cells by epithelial to mesenchymal transition events and signaling pathways
S100β-Positive Cells of Mesenchymal Origin Reside in the Anterior Lobe of the Embryonic Pituitary Gland
SOX10-positive cells emerge in the rat pituitary gland during late embryogenesis and start to express S100β
Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma
Differentiation capacities of PS-clusters, adult pituitary stem/progenitor cell clusters located in the parenchymal-niche, of the rat anterior lobe
Adamantinomatous and papillary craniopharyngiomas are characterized by distinct epigenomic as well as mutational and transcriptomic profiles
Mapping the distribution of stem/progenitor cells across the mouse middle ear during homeostasis and inflammation.
Expression of SRY-related HMG Box Transcription Factors (Sox) 2 and 9 in Craniopharyngioma Subtypes and Surrounding Brain Tissue
Complex integration of intrinsic and peripheral signaling is required for pituitary gland development
Major depletion of SOX2+ stem cells in the adult pituitary is not restored which does not affect hormonal cell homeostasis and remodelling
Can tissue biomarkers reliably predict the biological behavior of craniopharyngiomas? A comprehensive overview
SOX2 is sequentially required for progenitor proliferation and lineage specification in the developing pituitary
MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma
Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors
Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma
Localization of SOX2-positive stem/progenitor cells in the anterior lobe of the common marmoset (Callithrix jacchus) pituitary
Notch signaling in postnatal pituitary expansion: proliferation, progenitors, and cell specification
Single-Cell RNA Sequencing Reveals Novel Markers of Male Pituitary Stem Cells and Hormone-Producing Cell Types
Stem Cells in Pituitary Tumors: Experimental Evidence Supporting Their Existence and Their Role in Tumor Clinical Behavior
Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens-An Insight From Translational Studies
GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Clump formation in mouse pituitary-derived non-endocrine cell line Tpit/F1 promotes differentiation into growth-hormone-producing cells
Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target
SOX2 mediates crosstalk between Sonic Hedgehog and the Wnt/β-catenin signaling pathway to promote proliferation of pituitary adenoma cells
Lisa: inferring transcriptional regulators through integrative modeling of public chromatin accessibility and ChIP-seq data
Prenatal alcohol exposure increases the susceptibility to develop aggressive prolactinomas in the pituitary gland
Homeostatic and tumourigenic activity of SOX2+ pituitary stem cells is controlled by the LATS/YAP/TAZ cascade
Single-cell transcriptomic analysis of adult mouse pituitary reveals sexual dimorphism and physiologic demand-induced cellular plasticity
Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology
Identification of TGFβ-induced proteins in non-endocrine mouse pituitary cell line TtT/GF by SILAC-assisted quantitative mass spectrometry
Single-cell transcriptomics identifies divergent developmental lineage trajectories during human pituitary development
GFRα 1-2-3-4 co-receptors for RET Are co-expressed in Pituitary Stem Cells but Individually Retained in Some Adenopituitary Cells.
Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state.
Isolation of PRRX1-positive adult pituitary stem/progenitor cells from the marginal cell layer of the mouse anterior lobe.
SOX2 is required independently in both stem and differentiated cells for pituitary tumorigenesis in p27-null mice.
Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells.
Congenital Hypopituitarism During the Neonatal Period: Epidemiology, Pathogenesis, Therapeutic Options, and Outcome.
A human ACTH-secreting corticotroph tumoroid model: Novel Human ACTH-Secreting Tumor Cell in vitro Model.
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