Expression Profile of NOTCH3 in Mouse Spermatogonia

Okada, Ryu; Fujimagari, Megumi; Koya, Eri; Hirose, Yoshikazu; Satō, Tomomi; Nishina, Yasuzo

doi:10.1159/000481772

Cited by 11 publications

(10 citation statements)

References 38 publications

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“…It is worth mentioning that in mouse HES1 was detected in spermatogonia of immature testis. In adult mice the expression in spermatogonia decreased and HES1 was detected mainly in Sertoli cells [9,15,48]. In pubertal rats we found the expression of this protein in both spermatogonia and Sertoli cells.…”

Section: Discussionmentioning

confidence: 64%

“…Nevertheless, the presence of N1ICD and N2ICD and Notch effector genes in spermatogonia strongly suggest that Notch pathway is involved in the control of these cells. In addition, Okada et al [15] showed the expression of cleaved form of Notch3 receptor (N3ICD) and HES1 in prepubertal and adult mouse spermatogonia. Altogether, Notch signaling is clearly activated in spermatogonia via different Notch receptors, but whether each of them play specific role or they are functionally redundant remains to be explained.…”

Section: Discussionmentioning

confidence: 99%

“…During postnatal development of rodent testis changes in the pattern of Notch pathway components expression were observed; specifically Notch1 receptor replaces Notch3 in Sertoli cells of peripubertal mouse [9,14,15]. The role and regulation of Notch2 was demonstrated to date in fetal mouse testis [16] and in tumor Leydig cells [17], but only scarce data exist on its localization in seminiferous epithelium [18,19].…”

Section: Introductionmentioning

confidence: 99%

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Disruption of androgen signaling during puberty affects Notch pathway in rat seminiferous epithelium

Kamińska

Marek

Pardyak

et al. 2020

Reprod Biol Endocrinol

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Background: Onset of spermatogenesis at puberty is critically dependent on the activity of hypothalamic-pituitarygonadal axis and testosterone production by Leydig cells. The aim of this study was to examine whether activation of Notch receptors and expression of Notch ligands and effector genes in rat seminiferous epithelium are controlled by androgen signaling during puberty. Methods: Peripubertal (5-week-old) Wistar rats received injections of flutamide (50 mg/kg bw) daily for 7 days to reduce androgen receptor (AR) signaling or a single injection of ethanedimethane sulphonate (EDS; 75 mg/kg bw) to reduce testosterone production. Gene and protein expressions were analyzed by real-time RT-PCR and western blotting, respectively, protein distribution by immunohistochemistry, and steroid hormone concentrations by enzymelinked immunosorbent assay. Statistical analyses were performed using one-way ANOVA followed by Tukey's post hoc test or by Kruskal-Wallis test, followed by Dunn's test. Results: In both experimental models changes of a similar nature in the expression of Notch pathway components were found. Androgen deprivation caused the reduction of mRNA and protein expression of DLL4 ligand, activated forms of Notch1 and Notch2 receptors and HES1 and HEY1 effector genes (p < 0.05, p < 0.01, p < 0.001). In contrast, DLL1, JAG1 and HES5 expressions increased in seminiferous epithelium of both flutamide and EDS-treated rats (p < 0.05, p < 0.01, p < 0.001). Conclusions: Androgens and androgen receptor signaling may be considered as factors regulating Notch pathway activity and the expression of Hes and Hey genes in rat seminiferous epithelium during pubertal development. Further studies should focus on functional significance of androgen-Notch signaling cross-talk in the initiation and maintenance of spermatogenesis.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Disruption of androgen signaling during puberty affects Notch pathway in rat seminiferous epithelium

Kamińska

Marek

Pardyak

et al. 2020

Reprod Biol Endocrinol

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“…During postnatal development and along the spermatogenic cycle of adult male mouse, three Notch receptors (Notch 1-3) and ligands (Delta-like 1, 4 and Jagged 1, 2) were identified in the testis (Mori et al, 2003;Garcia & Hofmann, 2013;Murta et al, 2013;Okada et al, 2017;Kami nska et al, 2018). Although Notch receptors were identified both in germ and in Sertoli cells, Notch 1 signaling in adult seminiferous tubules is activated predominantly in Sertoli cells (Garcia & Hofmann, 2013;Liu et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Notch signaling regulates nuclear androgen receptor AR and membrane androgen receptor ZIP9 in mouse Sertoli cells

et al. 2019

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Background Notch signaling pathway is involved in contact‐dependent communication between the cells of seminiferous epithelium, and its proper activity is important for undisturbed spermatogenesis. Objectives The aim was to assess the effect of Notch pathway inhibition on the expression of nuclear (AR) and membrane (ZIP9) androgen receptors and androgen‐regulated genes, claudin‐5 and claudin‐11, in TM4 mouse Sertoli cell line. Materials and methods DAPT (γ‐secretase inhibitor) treatment and recombination signal binding protein silencing were employed to reduce Notch signaling, whereas immobilized ligands were used to activate Notch pathway in TM4 cells. To reveal specific effect of each androgen receptor, AR or ZIP9 silencing was performed. Results Notch pathway inhibition increased the expression of AR and ZIP9 mRNA and proteins (p < 0.01; p < 0.05) in TM4 cells, whereas incubation with Notch ligands, rDLL1 or rJAG1, reduced AR (p < 0.01; p < 0.001) and ZIP9 (p < 0.05; p < 0.01) expressions, respectively. Testosterone enhanced the expression of both receptors (p < 0.05; p < 0.01). Androgen‐regulated claudin‐5 and claudin‐11 (p < 0.01; p < 0.001) and cAMP (p < 0.001) were elevated in Notch‐inhibited cells, while activation of Notch signaling by DLL1 or JAG1 reduced claudin‐11 or claudin‐5 level (p < 0.01; p < 0.001), respectively. Discussion Our findings indicate opposite effect of Notch and androgen signaling on the expression of androgen receptors in TM4 cells. We demonstrated that AR expression is regulated by DLL1‐mediated Notch signaling, whereas JAG1 is involved in the regulation of ZIP9. The expression of both claudins and cAMP production is under inhibitory influence of Notch pathway. The effects of Notch signaling on claudin‐5 and claudin‐11 expression are mediated by ZIP9 and AR, respectively. Conclusion Notch signaling may be considered as an important pathway controlling Sertoli cell physiology, and its alterations may contribute to disturbed response of Sertoli cells to androgens.

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“…For example, NFYA is overexpressed in some cancers and its motif is related to meiosis-specific gene regulation [56][57][58] . Hes1 is expressed in prepubertal spermatogonia in mouse and SSEA+ human SSCs [59,60] . It can also promote EMT via the AKT pathway in cancers [61] .…”

Section: Dynamic Changes In Accessibility Of Regulatory Elements and mentioning

confidence: 99%

scATAC-Seq reveals epigenetic heterogeneity associated with an EMT-like process in male germline stem cells and its regulation by G9a

Liao

Suen

Luk

et al. 2020

Preprint

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Epithelial-mesenchymal transition (EMT) is a phenomenon in which epithelial cells acquire mesenchymal traits. It contributes to organogenesis and tissue homeostasis, as well as stem cell differentiation. Emerging evidence indicates that heterogeneous expression of EMT gene markers presents in sub-populations of germline stem cells (GSCs). However, the functional implications of such heterogeneity are largely elusive. Here, we unravelled an EMT-like process in GSCs by in vitro extracellular matrix (ECM) model and single-cell genomics approaches. Through modulating ECM, we demonstrated that GSCs exist in interconvertible epithelial-like and mesenchymal-like cell states. GSCs gained higher migratory ability after transition to a mesenchymal-like cell state, which was largely mediated by the TGF-β signaling pathway. Dynamics of epigenetic regulation at the single-cell level was also found to align with the EMT-like process. Chromatin accessibility profiles generated by single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) clustered GSCs into epithelial-like and mesenchymal-like states, which were associated with differentiation status. The high-resolution data revealed novel regulators in the EMT-like process, including transcription factors Zeb1 and Hes1. We further identified putative enhancer-promoter interactions and cis-co-accessibility networks at loci such as Tgfb1, Notch1 and Lin28a. Importantly, we demonstrated that histone methyltransferase G9a promoted the GSC EMT-like process in vitro and contributed to neonatal germ cell migration in vivo. Our work thus provides the foundation for understanding the EMT-like process and a comprehensive resource for future investigation of epigenetic regulatory networks in GSCs.

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Expression Profile of NOTCH3 in Mouse Spermatogonia

Cited by 11 publications

References 38 publications

Disruption of androgen signaling during puberty affects Notch pathway in rat seminiferous epithelium

Disruption of androgen signaling during puberty affects Notch pathway in rat seminiferous epithelium

Notch signaling regulates nuclear androgen receptor AR and membrane androgen receptor ZIP9 in mouse Sertoli cells

scATAC-Seq reveals epigenetic heterogeneity associated with an EMT-like process in male germline stem cells and its regulation by G9a

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