SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland

Fauquier, Teddy; Rizzoti, Karine; Dattani, Mehul; Lovell-Badge, Robin; Robinson, Iain C. A. F.

doi:10.1073/pnas.0707886105

Cited by 338 publications

(512 citation statements)

References 40 publications

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“…Rather, it is involved in a variety of fetal and adult stem cells, such as neural stem cells, retina and pituitary progenitor cells. [38][39][40][41] At the molecular level, Sox2 serves as a pioneer factor and is involved in cell fate determination through its dynamic interactions with different protein partners for transcriptional regulation of corresponding sets of target genes. [42][43][44][45] For example, in undifferentiated ES cells, Sox2 forms a heterodimer with Oct4 to activate stemness-related genes while repressing differentiationspecific genes.…”

Section: Discussionmentioning

confidence: 99%

Ube2s regulates Sox2 stability and mouse ES cell maintenance

et al. 2015

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Sox2 has a critical role in embryonic stem (ES) cell maintenance and differentiation. Interestingly, its activity is highly dosagedependent. Although transcriptional regulation of Sox2 has been extensively studied, the mechanisms orchestrating its degradation remain unclear. In this study, we identified ubiquitin-conjugating enzyme E2S (Ube2s) as a novel effector for Sox2 protein degradation. Ube2s mediates K11-linked polyubiquitin chain formation at the Sox2-K123 residue, thus marking it for proteasome-mediated degradation. Besides its role in fine-tuning the precise level of Sox2, Ube2s reinforces the self-renewing and pluripotent state of ES cells. Importantly, it also represses Sox2-mediated ES cell differentiation toward the neural ectodermal lineage.

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Section: Discussionmentioning

confidence: 99%

Ube2s regulates Sox2 stability and mouse ES cell maintenance

et al. 2015

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“…The recent characterization of pituitary stem cells (Fauquier et al 2008, Garcia-Lavandeira et al 2009, 2015, Vankelecom & Gremeaux 2010 implies the possibility of defining their mechanisms involved not only in pituitary cell renewal but also in pituitary tumorigenesis. Several groups have described the presence within the pituitary tumor of a side population containing cells with high efflux capacity and enriched with potentially tumor stem cells (Gleiberman et al 2008, Florio 2011, Mertens et al 2015.…”

Section: Autocrine Il-6 Mediates Pituitary Tumor Senescencementioning

confidence: 99%

Programmed cell senescence: role of IL-6 in the pituitary

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2017

Journal of Molecular Endocrinology

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IL-6 is a pleiotropic cytokine with multiple pathophysiological functions. As a key factor of the senescence secretome, it can not only promote tumorigenesis and cell proliferation but also exert tumor suppressive functions, depending on the cellular context. IL-6, as do other cytokines, plays important roles in the function, growth and neuroendocrine responses of the anterior pituitary gland. The multiple actions of IL-6 on normal and adenomatous pituitary function, cell proliferation, angiogenesis and extracellular matrix remodeling indicate its importance in the regulation of the anterior pituitary. Pituitary tumors are mostly benign adenomas with low mitotic index and rarely became malignant. Premature senescence occurs in slow-growing benign tumors, like pituitary adenomas. The dual role of IL-6 in senescence and tumorigenesis is well represented in pituitary tumor development, as it has been demonstrated that effects of paracrine IL-6 may allow initial pituitary cell growth, whereas autocrine IL-6 in the same tumor triggers senescence and restrains aggressive growth and malignant transformation. IL-6 is instrumental in promotion and maintenance of the senescence program in pituitary adenomas.

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“…Elsőként -az embrionális fejlődés 3-4. hetében -az oralis ectoderma egy jól körülírt szakasza megvastagodik [3].…”

Section: Az Adenohypophysis Embrionális Fejlődését Szabályozó Mechaniunclassified

Genetikai tényezők a hypopituitarismus kialakulásában. A transzkripciós faktorok szerepe az agyalapimirigy-elégtelenség hátterében

et al. 2018

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A hypothalamohypophysealis rendszer fejlődési rendellenességei klinikai megjelenésükben sokszínű hypophysiselég-telenséggel járhatnak. Ezen fejlődési rendellenességek jelentős részét a hypophysis organogenezisét szabályozó transzkripciós faktorok genetikai hibái okozhatják. Az agyalapi mirigy fejlődésének korai szakaszában expresszálódó transzkripciós faktorokat kódoló gének mutációi olyan összetett fejlődési rendellenességekhez vezethetnek, amelyekben a hypopituitarismushoz egyéb központi idegrendszeri malformációk is társulnak. Az organogenezis későbbi szakaszát szabályozó transzkripciós faktorok genetikai eltérései jellemzően többszörös, ritkán izolált agyalapi mirigy hormonhiányt okoznak extrahypophysealis manifesztáció nélkül. A hypophysistranszkripciós faktorok genetikai defektusainak azonosítása segítséget adhat a hormonhiányok előrejelzésében és az érintett családtagok szűrésében. Egyes hypophysistranszkripciós faktorok expressziója felnőttkorban is kimutatható, aminek fontos klinikai jelentősé-ge van a hypophysisadenomák WHO által ajánlott új rendszerű, ezen faktorok expresszióját is figyelembe vevő osztályozásában. Orv Hetil. 2018; 159(7): 278-284. Kulcsszavak: veleszületett hypopituitarismus, hypophysistranszkripciós faktorok, hypophysisadenoma Genetic factors in hypopituitarism. The role of transcription factors in pituitary hormone deficiencyDevelopmental disorders affecting the hypothalamic-pituitary system can result in pituitary hormone deficiency showing a diverse clinical presentation. A significant majority of these disorders are closely linked to defects in transcription factor genes which play a major role in pituitary development. Those affecting the early phase of organogenesis typically lead to complex conditions affecting the pituitary as well as structures in the central nervous system. Transcription factors involved in the late phase can result in combined but rarely isolated pituitary hormone deficiency without extra-pituitary manifestation. Identifying the defects in these pituitary transcription factor genes may provide a useful tool in predicting disease progression as well as screening family members. Several pituitary transcription factors can be detected in the adult gland as well which is strongly emphasized in the World Health Organization's most recent guideline for pituitary tumor classification. Our review summarizes the current essential knowledge relevant for clinical endocrinologists.

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SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland

Cited by 338 publications

References 40 publications

Ube2s regulates Sox2 stability and mouse ES cell maintenance

Ube2s regulates Sox2 stability and mouse ES cell maintenance

Programmed cell senescence: role of IL-6 in the pituitary

Genetikai tényezők a hypopituitarismus kialakulásában. A transzkripciós faktorok szerepe az agyalapimirigy-elégtelenség hátterében

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