scholarly journals Epigenetic regulator Lid maintains germline stem cells through regulating JAK-STAT signaling pathway activity

Biology Open ◽  
2015 ◽  
Vol 4 (11) ◽  
pp. 1518-1527 ◽  
Author(s):  
L. Tarayrah ◽  
Y. Li ◽  
Q. Gan ◽  
X. Chen
2015 ◽  
Vol 14 (5) ◽  
pp. 939-948 ◽  
Author(s):  
Lei ZHANG ◽  
Qi-sheng ZUO ◽  
Dong LI ◽  
Chao LIAN ◽  
Kamel E Ahmed ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Shiqin Li ◽  
Meng Wang ◽  
Yanghui Chen ◽  
Wei Wang ◽  
Junying Wu ◽  
...  

Germline stem cells (GSCs) are adult stem cells that are responsible for the production of gametes and include spermatogonial stem cells (SSCs) and ovarian germline stem cells (OGSCs). GSCs are located in a specialized microenvironment in the gonads called the niche. Many recent studies have demonstrated that multiple signals in the niche jointly regulate the proliferation and differentiation of GSCs, which is of significance for reproductive function. Previous studies have demonstrated that the hedgehog (Hh) signaling pathway participates in the proliferation and differentiation of various stem cells, including GSCs in Drosophila and male mammals. Furthermore, the discovery of mammalian OGSCs challenged the traditional opinion that the number of primary follicles is fixed in postnatal mammals, which is of significance for the reproductive ability of female mammals and the treatment of diseases related to germ cells. Meanwhile, it still remains to be determined whether the Hh signaling pathway participates in the regulation of the behavior of OGSCs. Herein, we review the current research on the role of the Hh signaling pathway in mediating the behavior of GSCs. In addition, some suggestions for future research are proposed.


2015 ◽  
Vol 37 (6) ◽  
pp. 2311-2322 ◽  
Author(s):  
Zezheng Pan ◽  
Mengli Sun ◽  
Jia Li ◽  
Fangyue Zhou ◽  
Xia Liang ◽  
...  

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.


2020 ◽  
Author(s):  
David Melamed ◽  
Daniel Kalderon

AbstractMany adult stem cells are maintained as a community by population asymmetry, wherein stochastic actions of individual cells collectively result in a balance between stem cell division and differentiation. We have used Drosophila Follicle Stem Cells (FSCs) as a paradigm to explore the extracellular niche signals that define a stem cell domain and organize stem cell behavior. FSCs produce transit-amplifying Follicle Cells (FCs) from their posterior face and quiescent Escort Cells (ECs) to their anterior. Here we show that JAK-STAT pathway activity, which declines from posterior to anterior, dictates the pattern of divisions over the FSC and EC domains, promotes more posterior FSC locations and conversion to FCs, while opposing EC production. A Wnt pathway gradient of opposite polarity promotes more anterior FSC locations and EC production and opposes FC production. Promotion of both FSC division and conversion to FCs by JAK-STAT signaling buffers the effects of genetically altered pathway activity on FSC numbers and balances the four-fold higher rate of differentiation at the posterior face of the FSC domain with a higher rate of FSC division in the most posterior layer. However, genetic elimination of Wnt pathway activity exacerbated elevated FC production resulting from increased JAK-STAT pathway activity, leading to rapid FSC depletion despite high rates of division. The two pathways combine to define a stem cell domain through concerted effects on FSC differentiation to ECs (high Wnt, low JAK-STAT) and FCs (low Wnt, high JAK-STAT) at each end of opposing signaling gradients, further enforced by quiescence at the anterior border due to declining JAK-STAT pathway activity.


2018 ◽  
Vol 234 (1) ◽  
pp. 915-926 ◽  
Author(s):  
Qijing Lei ◽  
Qin Pan ◽  
Na Li ◽  
Zhe Zhou ◽  
Juqing Zhang ◽  
...  

2017 ◽  
Vol 41 (3) ◽  
pp. 1051-1062 ◽  
Author(s):  
Haifeng Ye ◽  
Xiaoyan Li ◽  
Tuochen Zheng ◽  
Chuan Hu ◽  
Zezheng Pan ◽  
...  

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.


2021 ◽  
Author(s):  
Pradeep Kumar Bhaskar ◽  
Sheryl Southard ◽  
Kelly Baxter ◽  
Mark Van Doren

SummaryThe establishment of sexual identity in germ cells is critical for the development of male and female germline stem cells (GSCs) and production of sperm vs. eggs. Thus, this process is essential for sexual reproduction and human fertility. Germ cells depend on signals from the somatic gonad to determine their sex, but in organisms such as flies, mice and humans, the sex chromosome genotype of the germ cells is also important for germline sexual development. How somatic signals and germ cell-intrinsic cues act together to regulate germline sex determination is a key question about which little is known. We have found that JAK/STAT signaling in the GSC niche promotes male identity in germ cells and GSCs, in part by activating expression of the epigenetic reader Phf7. We have also found that JAK/STAT signaling is blocked in XX (female) germ cells through the intrinsic action of the sex determination gene Sex lethal, which preserves female identity. Thus, an important function of germline sexual identity is to control how GSCs respond to signals in their niche environment.


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