scholarly journals Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice

2015 ◽  
Vol 36 (5) ◽  
pp. 1712-1724 ◽  
Author(s):  
Jia Li ◽  
Fangyue Zhou ◽  
Tuochen Zheng ◽  
Zezheng Pan ◽  
Xia Liang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Signaling Pathway ◽  
Cell Biology ◽  
Control Group ◽  
Hippo Signaling ◽  
Germline Stem Cells ◽  
Hippo Signaling Pathway ◽  
Ovarian Cortex ◽  
Ovarian Aging

Background: The Hippo signaling pathway plays fundamental roles in stem cell maintenance in a variety of tissues and has thus implications for stem cell biology. Key components of this recently discovered pathway have been shown to be associated with primordial follicle activation. However, whether the Hippo signaling pathway plays a role in the development of Ovarian Germline Stem Cells (OGSCs) during physiological and pathological ovarian aging in mice is unknown. Methods: Mice at the age of 7 days (7D), or of 2, 10, or 20 months (2M, 10M, 20M) and mice at 2M treated with TPT and CY/BUS drugs were selected as physiological and pathological ovarian aging models, respectively. Immunohistochemistry was used to assess the development of follicles, and the co-localization of genes characteristic of OGSCs with MST1, LATS2 and YAP1 was assessed by immunofluorescence, western blotting and real-time PCR methods. Results: The Hippo signal pathway and MVH/OCT4 genes were co-expressed in the mouse ovarian cortex. The level and co-localization of LATS2, MST1, MVH, and OCT4 were significantly decreased with increased age, but YAP1 was more prevalent in the mouse ovarian cortex of 2M mice than 7D mice and was not observed in 20M mice. Furthermore, YAP1, MVH, and OCT4 were gradually decreased after TPT and CY/BUS treatment, and LATS2 mRNA and protein up-regulation persisted in TPT- and CY/BUS-treated mice. However, the expression of MST1 was lower in the TPT and CY/BUS groups compared with the control group. In addition, pYAP1 protein showed the highest expression in the ovarian cortexes of 7D mice compared with 20M mice, and the value of pYAP1/YAP1 decreased from 7D to 20M. Moreover, pYAP1 decreased in the TPT- and CY/BUS-treated groups, but the value of pYAP1/YAP1 increased in these groups. Conclusion: Taken together, our results show that the Hippo signaling pathway is associated with the changes that take place in OGSCs during physiological and pathological ovarian aging in mice. Thus, the Hippo signaling pathway may be involved in the development schedule of OGSCs.

scholarly journals The Hippo Signaling Pathway Regulates Ovarian Function via the Proliferation of Ovarian Germline Stem Cells

2017 ◽  
Vol 41 (3) ◽  
pp. 1051-1062 ◽  
Author(s):  
Haifeng Ye ◽  
Xiaoyan Li ◽  
Tuochen Zheng ◽  
Chuan Hu ◽  
Zezheng Pan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Mouse Models ◽  
Birth Rate ◽  
Ovarian Function ◽  
Reproductive Age ◽  
Hippo Signaling ◽  
Germline Stem Cells ◽  
Hippo Signaling Pathway ◽  
Proliferation And Differentiation

Objective: To improve the separation, identification and cultivation of ovarian germline stem cells (OGSCs), to clarify the relationship between the Hippo signaling pathway effector YAP1 and the proliferation and differentiation of OGSCs in vitro and to identify the major contribution of Hippo signaling to ovarian function. Methods: Two-step enzymatic separation processes and magnetic separation were used to isolate and identify OGSCs by determining the expression of Mvh, Oct4, Nanog, Fragilis and Stella markers. Then, YAP1, as the main effector molecule in the Hippo signaling pathway, was chosen as the target gene of the study. Lentivirus containing overexpressed YAP1 or a YAP1-targeted shRNA was transduced into OGSCs. The effects of modulating the Hippo signaling pathway on the proliferation, differentiation, reproduction and endocrine function of ovaries were observed by microinjecting the lentiviral vectors with overexpressed YAP1 or YAP1 shRNA into infertile mouse models or natural mice of reproductive age. Results: (1) The specific expression of Mvh, Oct4, Nanog, Fragilis and Stella markers was observed in isolated stem cells. Thus, the isolated cells were preliminarily identified as OGSCs. (2) The co-expression of LATS2, MST1, YAP1 and MVH was observed in isolated OGSCs. Mvh and Oct4 expression levels were significantly increased in OGSCs overexpressing YAP1 compared to GFP controls. Consistently, Mvh and Oct4 levels were significantly decreased in cells expressing YAP1-targeted shRNA. (3) After 14-75 days of YAP1 overexpression in infertile mouse models, we detected follicle regeneration in ovaries, the activation of primordial follicles and increased birth rate, accompanied by increasing levels of E2 and FSH. (4) However, we detected decreasing follicles in ovaries, lower birth rate, and decreasing E2 and FSH in serum from healthy mice of reproductive age following YAP1 shRNA expression. Conclusion: Methods for the isolation, identification and culture of OGSCs were successfully established. Further results indicate that isolated OGSCs can specifically recognize Hippo signaling molecules and that manipulation of YAP1 expression can be used to regulate the proliferation and differentiation of OGSCs, as well as ovarian function in mice. This study suggests that the Hippo signaling pathway may represent a new molecular target for the regulation of mouse ovarian functional remodeling.

scholarly journals The Hippo signaling pathway and stem cell biology

2012 ◽  
Vol 22 (7) ◽  
pp. 339-346 ◽  
Author(s):  
Azucena Ramos ◽  
Fernando D. Camargo
Keyword(s):  
Stem Cell ◽  
Signaling Pathway ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

scholarly journals The Hippo signaling pathway in stem cell biology and cancer

EMBO Reports ◽  
2014 ◽  
Vol 15 (6) ◽  
pp. 642-656 ◽  
Author(s):  
Jung‐Soon Mo ◽  
Hyun Woo Park ◽  
Kun‐Liang Guan
Keyword(s):  
Stem Cell ◽  
Signaling Pathway ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

scholarly journals Lats1/2-Mediated Alteration of Hippo Signaling Pathway Regulates the Fate of Bone Marrow-Derived Mesenchymal Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Lang Li ◽  
Liang Dong ◽  
Yifeng Wang ◽  
Xiuhong Zhang ◽  
Jie Yan
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Vertical Migration ◽  
Transduction Efficiency ◽  
Hippo Signaling ◽  
Migration Assay ◽  
Hippo Signaling Pathway ◽  
Low Expression

Bone marrow-derived mesenchymal stem cells (BMSCs) can be used to enhance lung repair in acute respiratory distress syndrome (ARDS); however, the repairing effect is limited by poor homing and retention of BMSCs. The purpose of this study was to investigate whether Lats1 and Lats2-mediated alteration of Hippo signaling pathway could promote the differentiation, proliferation, and migration of BMSCs. BMSCs were transduced by lentiviral vectors for high and low expression of Lats1 and Lats2. The expression levels of Lats1, Lats2, YAP, and 14-3-3, respectively, were assessed to clarify the regulatory effects of Lats1 and Lats2 on Hippo signaling. Osteogenic (Runx2 and OSX) and adipogenic (C/EBPα and PPAR-γ) transcription factors were determined to clarify the effects of Hippo signaling on BMSCs differentiation. The effects of Hippo signaling on BMSCs proliferation and horizontal and vertical migration were also measured by CCK-8, scratch assay, and Transwell migration assay, respectively. Lentiviral transduction efficiency could reach 93.11%–97.14%. High and low expression of Lats1 and Lats2 could activate and inhibit the Hippo signaling pathway, respectively. High and low expression of Lats1 and Lats2 could inhibit and promote BMSCs differentiation into osteoblasts and adipocytes. High and low expression of Lats1 and Lats2 could inhibit and promote BMSCs proliferation and horizontal and vertical migration, respectively. Our studies suggest that Lats1/2-meidiated inhibition of Hippo signaling in BMSCs may optimize their effects of tissue repair in ARDS, suggesting a novel strategy for enhancing disease therapeutics.

GNAS knockdown suppresses osteogenic differentiation of mesenchymal stem cells via activation of Hippo signaling pathway

2019 ◽  
Vol 234 (12) ◽  
pp. 22299-22310 ◽  
Author(s):  
Jiangdong An ◽  
Guangjie Li ◽  
Jin Zhang ◽  
Haiyu Zhou ◽  
Jin Jiang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

scholarly journals The Expression of Markers Related to Ovarian Germline Stem Cells in the Mouse Ovarian Surface Epithelium and the Correlation with Notch Signaling Pathway

2015 ◽  
Vol 37 (6) ◽  
pp. 2311-2322 ◽  
Author(s):  
Zezheng Pan ◽  
Mengli Sun ◽  
Jia Li ◽  
Fangyue Zhou ◽  
Xia Liang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Ovarian Surface Epithelium ◽  
Notch Signaling Pathway ◽  
Surface Epithelium ◽  
Stem Cell Markers ◽  
Germline Stem Cells ◽  
Ovarian Surface

Background/Aims: Ovarian germline stem cells (OGSCs) have been shown to mainly exist in the ovarian surface epithelium (OSE), but the activity changes of germline stem cells during different reproductive stages and the potential regulatory signaling pathway are still unknown. The Notch signaling pathway plays a key role in cell development, primordial follicles and stem cell proliferation. However, whether it plays a role in the proliferation of OGSCs is unknown. Here, we analyzed the activity changes of germline stem cells and the correlation between germline stem cells and the Notch signaling pathway. Methods: The expression of germline stem cell markers Mvh, Ooc4 and the Notch molecules Notch1, Hes1, and Hes5 were detected during 3 days (3d), and 2, 12, 20 months (2m, 12m, 20m) mouse ovarian surface epithelium samples. DAPT, a specific inhibitor of the Notch pathway, was used to observe the influence of Notch signaling in the germline stem cells. Results: The results showed that the levels of MVH and OCT4 decreased substantially with reproductive age in ovarian surface epithelium, and the same tendency was detected in the Notch signaling molecules Notch1, Hes1 and Hes5. Dual-IF results showed that the germline stem cell markers were co-expressed with Notch molecules in the ovarian surface epithelium. While, the expression of MVH and OCT4 were reduced when the ovaries were treated with DAPT and the levels were attenuated with increasing dose of DAPT. Conclusion: Taken together, our results indicate that the viability of OGSCs decreased with the age of the mouse ovaries, and the activity of OGSCs in the ovarian surface epithelium may be related to the Notch signaling pathway.

Abstract 3662: Honokiol affects stem cell viability in part through suppression of Hippo signaling pathway.

2013 ◽  
Author(s):  
Dharmalingam Subramaniam ◽  
Sivapriya Ponnurangam ◽  
Shahid Umar ◽  
Satish Ramalingam ◽  
Roy A. Jensen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway
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