S100β-Positive Cells of Mesenchymal Origin Reside in the Anterior Lobe of the Embryonic Pituitary Gland

Horiguchi, Kotaro; Yako, Hideji; Yoshida, Saishu; Fujiwara, Ken; Tsukada, Takehiro; Kanno, Noriatsu; Ueharu, Hiroki; Nishihara, Hiroto; Katō, Takako; Yashiro, Takashi; Kato, Yukio

doi:10.1371/journal.pone.0163981

Cited by 17 publications

(13 citation statements)

References 57 publications

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“…To maintain the physiological functions of the pituitary, a blood capillary network composed of endothelial cells and pericytes is essential. We have observed in the developing pituitary gland that S100β/isolectin B4-double positive cells, which may be endothelial-like cells, appear to enter into the embryonic anterior lobe 30 . A portion of S100β-positive cells extend their cytoplasmic processes into the basement membrane around blood capillaries 31 .…”

Section: Discussionmentioning

confidence: 72%

Isolation and characterisation of CD9-positive pituitary adult stem/progenitor cells in rats

Horiguchi

Fujiwara

Yoshida

et al. 2018

Sci Rep

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S100β protein and SOX2-double positive (S100β/SOX2-positive) cells have been suggested to be adult pituitary stem/progenitor cells exhibiting plasticity and multipotency. The aim of the present study was to isolate S100β/SOX2-positive cells from the adult anterior lobes of rats using a specific antibody against a novel membrane marker and to study their characteristics in vitro. We found that cluster of differentiation (CD) 9 is expressed in the majority of adult rat S100β/SOX2-positive cells, and we succeeded in isolating CD9-positive cells using an anti-CD9 antibody with a pluriBead-cascade cell isolation system. Cultivation of these cells showed their capacity to differentiate into endothelial cells via bone morphogenetic protein signalling. By using the anterior lobes of prolactinoma model rats, the localisation of CD9-positive cells was confirmed in the tumour-induced neovascularisation region. Thus, the present study provides novel insights into adult pituitary stem/progenitor cells involved in the vascularisation of the anterior lobe.

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Section: Discussionmentioning

confidence: 72%

Isolation and characterisation of CD9-positive pituitary adult stem/progenitor cells in rats

Horiguchi

Fujiwara

Yoshida

et al. 2018

Sci Rep

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“…In summary, we revealed the characteristics of SOX2-positive stem/progenitor cell populations in the pituitary gland of SDRs, especially in the MCL. It has been reported that S100β-positive cells migrate from the intermediate lobe to the anterior lobe [ 17 , 18 ]. The results of this study suggested that GH-producing cells not only secrete hormones to stimulate growth and work for lipolysis but were also involved in attracting adult pituitary stem/progenitor cells to the MCL of the anterior lobe.…”

Section: Discussionmentioning

confidence: 99%

Characterization of pituitary stem/progenitor cell populations in spontaneous dwarf rats

Sasaki

Higuchi

2022

The Journal of Veterinary Medical Science

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Spontaneous dwarf rat (SDR) is a primary experimental animal model for the study of pituitary dwarfism with a point mutation in the Gh gene encoding growth hormone (GH). In previous studies, SDR has been reported to be associated with the GH deficiency as well as combined hormone deficiencies, the cause of which is unknown. In this study, we focused on the characteristics of pituitary stem/progenitor cell populations, which are a source of hormone-producing cells, in SDR. Immunofluorescence and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses confirmed the defects in GH-producing cells, the decreased number of prolactin- and thyroid-stimulating hormone-producing cells, and the increased number of adrenocorticotropic hormone- and luteinizing hormone-producing cells. Additionally, qRT-PCR analysis showed increased Prop1 (an embryonic stem/progenitor cell marker) expression and decreased S100b (a putative adult stem/progenitor cell marker) expression in SDRs. In the pituitary stem/progenitor cell niche, the marginal cell layer, the proportion of SOX2/PROP1-double positive cells was higher in adult SDRs than in adult Sprague Dawley (SD) rats but that of SOX2/S100β-double positive cells was much lower. Furthermore, the number of SOX2/PROP1-double positive cells in SD rats significantly decreased with growth; however, the decrease was smaller in SDRs. In contrast, the number of SOX2/S100β-double positive cells in SD rats significantly increased with growth; however, they were few in SDRs. Thus, S100β-positive pituitary stem/progenitor cells failed to settle in pituitary dwarfism with the Gh gene mutation, leading to multiple hypopituitarism including GH deficiency.

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“…However, as the proportion of CD9/Ki67-positive cells in the IL-side MCL decreased, it is still unclear how the CD9/SOX2-positive cells in the IL-side MCL supply PRL cells to the AL during pregnancy and lactation, while their self-proliferation activity is low. Some reports show migration of stem/progenitor cells from outside the pituitary gland [ 19 , 20 , 21 ], however, further analysis is needed to identify the origin of CD9/SOX2-positive cells in the IL-side MCL.…”

Section: Discussionmentioning

confidence: 99%

Differentiation of stem progenitor CD9/SOX2-positive cells is promoted with increased prolactin-producing and endothelial cells in the pituitary

Horiguchi

Fujiwara

Tsukada

et al. 2022

Journal of Reproduction and Development

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Sex-determining region Y-box 2 (SOX2)-positive cells are stem/progenitor cells in the adenohypophysis, comprising the anterior and intermediate lobes (AL and IL, respectively). The cells are located in the marginal cell layer (MCL) facing Rathke’s cleft (primary niche) and the parenchyma of the AL (secondary niche). We previously demonstrated in vitro that the tetraspanin superfamily CD9 and SOX2 double-positive (CD9/SOX2-positive) cells in the IL-side MCL migrate to the AL side and differentiate into hormone-producing and endothelial cells in the AL parenchyma. Here, we performed in vivo studies to evaluate the role of IL-side CD9/SOX2-positive cells in pregnancy, lactation, and treatment with diethylstilbestrol (DES; an estrogen analog) when an increased population of prolactin (PRL) cells was observed in the AL of the rat pituitary. The proportions of CD9/SOX2-, CD9/Ki67-, and PRL/TUNEL-positive cells decreased in the primary and secondary niches during pregnancy and DES treatment. In contrast, the number of CD9/PRL-positive cells increased in the AL-side MCL and AL parenchyma during pregnancy and during DES treatment. The proportion of PRL/Ki67-positive cells increased in the AL-side MCL and AL parenchyma in response to DES treatment. Next, we isolated CD9-positive cells from the IL-side MCL using an anti-CD9 antibody. During cell culture, the cells formed free-floating three-dimensional clusters (pituispheres). Furthermore, CD9-positive cells in the pituisphere differentiated into PRL cells, and their differentiation potential was promoted by DES. These findings suggest that CD9/SOX2-positive cells in the IL-side MCL may act as adult stem cells in the AL parenchyma that supply PRL cells under the influence of estrogen.

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S100β-Positive Cells of Mesenchymal Origin Reside in the Anterior Lobe of the Embryonic Pituitary Gland

Cited by 17 publications

References 57 publications

Isolation and characterisation of CD9-positive pituitary adult stem/progenitor cells in rats

Isolation and characterisation of CD9-positive pituitary adult stem/progenitor cells in rats

Characterization of pituitary stem/progenitor cell populations in spontaneous dwarf rats

Differentiation of stem progenitor CD9/SOX2-positive cells is promoted with increased prolactin-producing and endothelial cells in the pituitary

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