Distinct Developmental Roles of Cell Cycle Inhibitors p57<sup>Kip2</sup> and p27<sup>Kip1</sup> Distinguish Pituitary Progenitor Cell Cycle Exit from Cell Cycle Reentry of Differentiated Cells

Bilodeau, Steve; Roussel-Gervais, Audrey; Drouin, Jacques

doi:10.1128/mcb.01885-08

Cited by 115 publications

(141 citation statements)

References 47 publications

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“…The NOTCH pathway is another essential regulator of pituitary embryogenesis (Kita et al 2007;Monahan et al 2009;Raetzman et al 2004;Zhu et al 2005Zhu et al , 2007, of which several components are upregulated in the adult (mouse) pituitary stem cell fraction (Chen et al 2006(Chen et al , 2009Vankelecom 2010) and are found expressed in some of the MZ and parenchymal S100 þ cells of the (rat) AP (Tando et al 2013). Some other transcriptional regulators that play an important role in pituitary embryonic development (such as Hesx1, the earliest known gene expressed in the pituitary primordium, Lhx4, Pax6, Otx2, Ascl1 and the Six/Eya/ Dach genes; Kelberman et al 2009;Zhu et al 2005Zhu et al , 2007 are also higher transcribed in the adult pituitary stem cell fraction (Chen et al 2006(Chen et al , 2009reviewed in Vankelecom 2010reviewed in Vankelecom , 2012, as well as the cyclin-dependent kinase inhibitor p57 that, during embryogenesis, emerges in the RP progenitor cells that stop cycling to embark on differentiation (Bilodeau et al, 2009;Vankelecom 2010;Vankelecom and Chen 2014). Finally, components of the fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) pathways, having important roles in the specification and proliferation of RP progenitor cells (Ericson et al 1998;Zhu et al 2005Zhu et al , 2007, are also upregulated in the adult stem cells (Vankelecom 2010;Vankelecom and Chen 2014).…”

Section: Pituitary Stem Cells: Expanding Molecular Portrayalmentioning

confidence: 99%

Pituitary Stem Cells: Quest for Hidden Functions

Vankelecom

2016

Stem Cells in Neuroendocrinology

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The pituitary is the core endocrine gland, ruling fundamental processes of body growth, metabolism, reproduction and stress. Over the past decade, it has progressively become clear that the pituitary, like many adult tissues, harbors a population of stem cells. While the molecular depiction of these cells is constantly expanding, their function remains essentially hidden. From recent studies, the picture is developing that the stem cells of the adult pituitary are highly quiescent and mainly come into play during pathological conditions.Upon transgenic cell-ablation damage in the pituitary, the stem cell compartment is promptly turned on with expansion and expression of the missing hormone. This activation is accompanied by substantial regeneration of the lost hormonal cells, a restorative competence that was unexpected in the mature gland. This regenerative skill, however, rapidly disappears with aging, together with a decline in the number and fitness of the stem cells. One function of the adult pituitary stem cells may thus be hidden in the regenerative toolbox of the gland, at least during a specified and limited time window.Recent work also showed activation of the pituitary stem cell compartment during tumor formation in the (mouse) gland. Moreover, pituitary tumors (from patients and mice) contain a candidate 'tumor stem cell' (TSC) population. The pathogenetic steps of initiation, expansion, invasion and recurrence of pituitary tumors remain far from understood. A link between the tumor-driving TSC and the pituitary stem cells may shed new light on this tumorigenic darkness.To conclude, decoding the hidden functions of pituitary stem cells will not only lead to better fundamental insights into their role but may also expose (novel) targets for treating pituitary tumors and for regenerative intervention in pituitary deficiency, as caused by damage, tumors or aging. Yet, the journey in the 'hidden valley' of pituitary stem cell functions has only just begun, and a long distance still has to be walked.

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Section: Pituitary Stem Cells: Expanding Molecular Portrayalmentioning

confidence: 99%

Pituitary Stem Cells: Quest for Hidden Functions

Vankelecom

2016

Stem Cells in Neuroendocrinology

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“…RP contains the embryonic precursors of the pituitary gland that generate all of the hormone-producing cells of the anterior pituitary (Bilodeau et al 2009, Davis et al 2011, Jayakody et al 2012. Based on patterns of cytokeratin expression, it has been suggested that ACP may derive from remnants of RP epithelium in humans.…”

Section: Human Tumourmentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: Biology of human craniopharyngioma: lessons from mouse models

Martinez-Barbera¹

2015

Journal of Endocrinology

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Adamantinomatous craniopharyngiomas (ACP) are clinically relevant tumours that are associated with high morbidity, poor quality of life and occasional mortality. Human and mouse studies have provided important insights into the biology of these aggressive tumours, and we are starting to understand why, how and when these tumours develop in humans. Mutations in b-catenin that result in the over-activation of the WNT/b-catenin signalling pathway are critical drivers of most, perhaps of all, human ACPs. Mouse studies have shown that only pituitary embryonic precursors or adult stem cells are able to generate tumours when targeted with oncogenic b-catenin, which suggests that the cell context is critical in order for mutant b-catenin to exert its oncogenic effect. Interestingly, mutant stem cells do not generate the bulk of the tumour cells; instead, they induce tumours in a paracrine manner. Combining basic studies in mice and humans will provide further insights into the biology of these neoplasms and will reveal pathogenic pathways that could be targeted with specific inhibitors for the benefit of patients. These benign tumours may additionally represent a unique model for investigating the early steps that lead to oncogenesis.

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“…A similar cell fate switch is observed in the AL and the cells that have switched are marked by expression of the gonadotroph-specific factor SF1. Further, cells that fail to complete that cell fate switch remain in somewhat of a limbo between progenitor and differentiated status as revealed by the coexpression of two cell cycle inhibitors, p57 Kip1 and p27 Kip2 , the former normally marking only pituitary progenitors that recently exited the cell cycle and progenitor state, and the latter marking differentiated cells (Bilodeau et al 2009). …”

Section: Tpit a Tbox Tf Restricted To Pomc Lineagesmentioning

confidence: 99%

60 YEARS OF POMC: Transcriptional and epigenetic regulation of POMC gene expression

Drouin

2016

Journal of Molecular Endocrinology

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Expression of the pro-opiomelanocortin (POMC) gene integrates numerous inputs that reflect the developmental history of POMC-expressing cells of the pituitary and hypothalamus, as well as their critical role in the endocrine system. These inputs are integrated at specific regulatory sequences within the promoter and pituitary or hypothalamic enhancers of the POMC locus. Investigations of developmental mechanisms and transcription factors (TFs) responsible for pituitary activation of POMC transcription led to the discovery of the Pitx factors that have critical roles in pituitary development and striking patterning functions in embryonic development. Terminal differentiation of the two pituitary POMC lineages, the corticotrophs and melanotrophs, is controlled by Tpit; mutations of the human TPIT gene cause isolated adrenocorticotrophic hormone deficiency. Intermediate lobe and melanotroph identity is provided by the pioneer TF Pax7 that remodels chromatin to reveal a new repertoire of enhancers for Tpit action. Many signaling pathways regulate POMC transcription including activation by hypothalamic corticotrophin-releasing hormone acting through the orphan nuclear receptors of the Nur family and feedback repression by glucocorticoids and their glucocorticoid receptor. TFs of the basic helix-loop-helix, Smad, Stat, Etv, and nuclear factor-B families also mediate signals for control of POMC transcription. Whereas most of these regulatory processes are conserved in different species, there are also notable differences between specific targets for regulation of the human compared with mouse POMC genes.

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Distinct Developmental Roles of Cell Cycle Inhibitors p57^Kip2 and p27^Kip1 Distinguish Pituitary Progenitor Cell Cycle Exit from Cell Cycle Reentry of Differentiated Cells

Cited by 115 publications

References 47 publications

Pituitary Stem Cells: Quest for Hidden Functions

Pituitary Stem Cells: Quest for Hidden Functions

60 YEARS OF NEUROENDOCRINOLOGY: Biology of human craniopharyngioma: lessons from mouse models

60 YEARS OF POMC: Transcriptional and epigenetic regulation of POMC gene expression

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Distinct Developmental Roles of Cell Cycle Inhibitors p57Kip2 and p27Kip1 Distinguish Pituitary Progenitor Cell Cycle Exit from Cell Cycle Reentry of Differentiated Cells

Cited by 115 publications

References 47 publications

Pituitary Stem Cells: Quest for Hidden Functions

Pituitary Stem Cells: Quest for Hidden Functions

60 YEARS OF NEUROENDOCRINOLOGY: Biology of human craniopharyngioma: lessons from mouse models

60 YEARS OF POMC: Transcriptional and epigenetic regulation of POMC gene expression

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Distinct Developmental Roles of Cell Cycle Inhibitors p57^Kip2 and p27^Kip1 Distinguish Pituitary Progenitor Cell Cycle Exit from Cell Cycle Reentry of Differentiated Cells