PROP1 coexists with SOX2 and induces PIT1-commitment cells

Yoshida, Saishu; Katō, Takako; Sugiyama, Takao; Lv, Cai; Nakayama, Michie; Kato, Yukio

doi:10.1016/j.bbrc.2009.05.027

Cited by 81 publications

(118 citation statements)

References 16 publications

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“…The observation that Prx2 is present in some gonadotropes may lend support to the idea that Prx2 has a transient role in differentiating pituitary cells. More recently, we have reported that Prop1 is present in the stem/progenitor cells of embryonic pituitaries [50] and found that Prx2 is present in the Prop1-positive cells (unpublished observation). To clarify the role of Prx2, we are currently attempting to confirm the localization of Prx2-positive cells during rat pituitary development, and the results will be described elsewhere.…”

Section: Prx2mentioning

confidence: 74%

Molecular Cloning of Paired Related Homeobox 2 (Prx2) as a Novel Pituitary Transcription Factor

Sugiyama

Ishikawa

Katō

et al. 2009

Journal of Reproduction and Development

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Abstract. This study aimed to identify protein(s) that bind(s) to the highly AT-rich sequence of porcine Fshb promoter region -852/-746 (named Fd2) by the Yeast One-Hybrid Cloning System and finally a paired related homeodomain transcription factor, Prx2, known as a key factor for skeletogenesis was cloned. RT-PCR analysis of fetal and postnatal porcine pituitaries demonstrated that Prx2 starts to be expressed at around fetal days 40-50 just before the beginning of Lhb-expression and that the level of Prx2 increases after birth. Immunohistochemical analysis of the prepubertal porcine pituitary revealed that some Prx2-positive cells overlap some Lhβ-positive cells. Transient transfection assay using nonpituitary CHO cells and pituitary tumor-derived LβT2 cells revealed that Prx2 plays a cell-type dependent role in modulation of the Fshb promoter, showing stimulation in CHO cells and repression in LβT2 cells via the regions of Fd2 and -596/-239. The binding ability of Prx2 to the regions of Fd2 and -596/-239 was confirmed by electrophoretic mobility shift assay. DNase I footprinting revealed that broad regions of Fd2 were bound by Prx2 and that -596/-239 contained seven Prx2-binding sites. The SELEX method using a random N15-mer oligonucleotide pool demonstrated that Prx2 monomer binds to a TAATT motif, which is present in Fd2 and -596/-239. However, the binding of Prx2 to TAATT with a single molecule and its inverted repeat with two molecules could not induce transcriptional activation, indicating that the Prx2-dependent transcriptional modulation demonstrated in cultured cells is not introduced by Prx2 alone. Thus, this study demonstrated for the first time that Prx2 is expressed in the pituitary gland and at least in a part of gonadotropes in which Prx2 may play a role in repression of the Fshb gene. Key words: Follicle-stimulating hormone (FSH), Gonadotropin, Pituitary, Prx2, Transcription factor (J. Reprod. Dev. 55: [502][503][504][505][506][507][508][509][510][511] 2009) ollicle-stimulating hormone (FSH), in addition to luteinizing hormone (LH) and thyroid-stimulating hormone (TSH), is a member of the pituitary glycoprotein hormone family consisting of a common α subunit (αGSU) and a noncovalently associated hormone-specific β subunit and plays crucial roles in folliculogenesis in females and spermatogenesis in males. Notably, three gonadotropin subunit genes, Cga, Fshb and Lhb, are expressed in the same pituitary cell, the gonadotrope. Several investigations have been conducted to clarify the specific regulatory mechanism of Cga and two β subunit genes (reviewed in Refs. [1] We have previously observed that plural nuclear proteins specifically bind to the AT-rich sequence of the porcine Fshb promoter region -852/-746 (named Fd2) [10], and have demonstrated that the upstream region -852/+10 containing Fd2 is sufficient for gonadotrope-specific expression [11]. Cloning by the Yeast OneHybrid System using Fd2 as a bait sequence led us to select plural proteins including Prop1 and Lhx2 [12,13]. At the same t...

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Section: Prx2mentioning

confidence: 74%

Molecular Cloning of Paired Related Homeobox 2 (Prx2) as a Novel Pituitary Transcription Factor

Sugiyama

Ishikawa

Katō

et al. 2009

Journal of Reproduction and Development

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Section: Pituitary Stem Cells: Expanding Molecular Portrayalmentioning

confidence: 99%

“…This transcription factor, which -among others -is essential for the regulation and migration of RP progenitor cells during pituitary embryogenesis (Himes and Raetzman 2009;Ward et al 2005;Zhu et al 2005Zhu et al , 2007, is expressed in the SOX2 þ cells, although it is not clear yet whether postnatal expression in the MZ stops after the first postnatal weeks or is continuous throughout life (Garcia-Lavandeira et al 2009;Yoshida et al 2009Yoshida et al , 2011. In general, there is no co-localization of PROP1 or SOX2 with hormones (Chen et al 2009;Fauquier et al 2008;Fu et al 2012a,b;Garcia-Lavandeira et al 2009;Gremeaux et al 2012;Yoshida et al 2009), supporting the general notion that stem cell conservators must be downregulated before differentiation starts. 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).…”

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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“…This side population has since been described for pituitaries of other vertebrates (Chen et al 2005(Chen et al , 2006van Rijn et al 2012). In time, additional markers of cells with this in vitro self-renewal capacity have been put forward to refine the characterisation of PSCs, including Nestin, PROP1, SOX9, GFRα2 and PRX1/2 (Gleiberman et al 2008;Yoshida et al 2009;Rizzoti et al 2013;GarciaLavandeira et al 2009;Higuchi et al 2014). In the postnatal rodent gland in vivo, SOX2-positive cells displayed a high degree of overlap with other proposed stem cell markers such as SOX9 (Rizzoti et al 2013), PROP1 (Yoshida et al 2009(Yoshida et al , 2011, and PRX1/2 (Higuchi et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…In time, additional markers of cells with this in vitro self-renewal capacity have been put forward to refine the characterisation of PSCs, including Nestin, PROP1, SOX9, GFRα2 and PRX1/2 (Gleiberman et al 2008;Yoshida et al 2009;Rizzoti et al 2013;GarciaLavandeira et al 2009;Higuchi et al 2014). In the postnatal rodent gland in vivo, SOX2-positive cells displayed a high degree of overlap with other proposed stem cell markers such as SOX9 (Rizzoti et al 2013), PROP1 (Yoshida et al 2009(Yoshida et al , 2011, and PRX1/2 (Higuchi et al 2014). We confirmed that SOX2-positive cells did not overlap with differentiation markers but we sought to determine if they were able to give rise to all the differentiated lineages in vivo.…”

Section: Introductionmentioning

confidence: 99%

Pituitary Stem Cells During Normal Physiology and Disease

Andoniadou

2016

Stem Cells in Neuroendocrinology

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Summary The homeostatic maintenance and functional modification of tissues require a combination of regulated proliferation and differentiation by somatic stem cells and more committed progenitors. Of relevance to regenerative medicine approaches, the endogenous stimulation of cell types for replenishment of damaged tissues requires an understanding of the signals that promote proliferation and direct appropriate differentiation to specialised cell types. We recently showed that pituitary stem cells expressing the transcription factor SOX2 are able to contribute to the generation of new hormone-producing cells during postnatal life. The signals controlling proliferation in the anterior pituitary are poorly understood and little is known about the influences supporting the choices between proliferation and quiescence among stem cells. The WNT signalling pathway is a major regulator of proliferation and influences stem cells in multiple tissues throughout the body as well as cancer stem cells in tumorigenesis. Forced up-regulation of the WNT pathway specifically in SOX2-positive pituitary stem cells by transgenic approaches in mouse stimulates a transient burst of proliferation, maintaining their uncommitted phenotype. These mutated stem cells subsequently induce tumorigenesis in a non-cell autonomous manner, as they promote proliferation of surrounding cell types through the secretion of paracrine factors. The studies presented here aim to provide insights into pituitary stem cell behaviour and their possible roles during disease states."If there were no regeneration there could be no life. If everything regenerated there would be no death. All organisms exist between these two extremes." Richard J. Goss, Principles of Regeneration (1969).

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PROP1 coexists with SOX2 and induces PIT1-commitment cells

Cited by 81 publications

References 16 publications

Molecular Cloning of Paired Related Homeobox 2 (Prx2) as a Novel Pituitary Transcription Factor

Molecular Cloning of Paired Related Homeobox 2 (Prx2) as a Novel Pituitary Transcription Factor

Pituitary Stem Cells: Quest for Hidden Functions

Pituitary Stem Cells During Normal Physiology and Disease

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