GSK3 inhibitor-BIO regulates proliferation of female germline stem cells from the postnatal mouse ovary

Circular RNAs (circRNAs) play important roles in the self-renewal of stem cells. However, their significance and regulatory mechanisms in female germline stem cells (FGSCs) are largely unknown. Here, we identified an N6-methyladenosine (m6A)-modified circRNA, circGFRα1, which is highly abundant in mouse ovary and stage-specifically expressed in mouse FGSC development. Knockdown of circGFRα1 in FGSCs significantly reduced their self-renewal. In contrast, overexpression of circGFRα1 enhanced FGSC self-renewal. Mechanistically, circGFRα1 promotes FGSC self-renewal by acting as a competing endogenous RNA (ceRNA) that sponges miR-449, leading to enhanced GFRα1 expression and activation of the glial cell derived neurotrophic factor (GDNF) signaling pathway. Furthermore, circGFRα1 acts as a ceRNA based on METTL14-mediated cytoplasmic export through the GGACU motif. Our study should help to understand the mechanisms regulating germ cell development, add new evidence on the mechanism of action of circRNA, and deepen our understanding of the development of FGSCs.

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How Can Female Germline Stem Cells Contribute to the Physiological Neo-Oogenesis in Mammals and Why Menopause Occurs?

Microscopy and Microanalysis ◽

10.1017/s143192761000036x ◽

2010 ◽

Vol 17 (4) ◽

pp. 498-505 ◽

Cited By ~ 11

Author(s):

Antonin Bukovsky

Keyword(s):

Stem Cells ◽

Adult Mouse ◽

Mammalian Species ◽

Reproductive Period ◽

Germline Stem Cells ◽

Environmental Threats ◽

Ovarian Stem Cells ◽

Lower Vertebrates ◽

Female Germline ◽

Prevailing View

AbstractAt the beginning of the last century, reproductive biologists have discussed whether in mammalian species the fetal oocytes persist or are replaced by neo-oogenesis during adulthood. Currently the prevailing view is that neo-oogenesis is functional in lower vertebrates but not in mammalian species. However, contrary to the evolutionary rules, this suggests that females of lower vertebrates have a better opportunity to provide healthy offspring compared to mammals with oocytes subjected to environmental threats for up to several decades. During the last 15 years, a new effort has been made to determine whether the oocyte pool in adult mammals is renewed as well. Most recently, Ji Wu and colleagues reported a production of offspring from female germline stem cells derived from neonatal and adult mouse ovaries. This indicates that both neonatal and adult mouse ovaries carry stem cells capable of producing functional oocytes. However, it is unclear whether neo-oogenesis from ovarian somatic stem cells is physiologically involved in follicular renewal and why menopause occurs. Here we review observations that indicate an involvement of immunoregulation in physiological neo-oogenesis and follicular renewal from ovarian stem cells during the prime reproductive period and propose why menopause occurs in spite of persisting ovarian stem cells.

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A new tool to generate transgenic rats using female germline stem cells from post-natal ovaries

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gau017 ◽

2014 ◽

Vol 20 (4) ◽

pp. 283-285 ◽

Cited By ~ 5

Author(s):

Y. Pan

Keyword(s):

Stem Cells ◽

Germline Stem Cells ◽

Transgenic Rats ◽

Female Germline

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Comparison of different in vitro differentiation conditions for murine female germline stem cells

Cell Proliferation ◽

10.1111/cpr.12530 ◽

2018 ◽

Vol 52 (1) ◽

pp. e12530 ◽

Cited By ~ 7

Author(s):

Kang Zou ◽

Jian Wang ◽

Haiwei Bi ◽

Yabin Zhang ◽

Xueli Tian ◽

...

Keyword(s):

Stem Cells ◽

Germline Stem Cells ◽

In Vitro Differentiation ◽

Female Germline

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Endocrine regulation of female germline stem cells in the fruit fly Drosophila melanogaster

Current Opinion in Insect Science ◽

10.1016/j.cois.2018.07.001 ◽

2019 ◽

Vol 31 ◽

pp. 14-19 ◽

Cited By ~ 4

Author(s):

Yuto Yoshinari ◽

Yoshitomo Kurogi ◽

Tomotsune Ameku ◽

Ryusuke Niwa

Keyword(s):

Stem Cells ◽

Drosophila Melanogaster ◽

Fruit Fly ◽

Endocrine Regulation ◽

Germline Stem Cells ◽

Female Germline

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Production of Zebrafish Offspring from Cultured Female Germline Stem Cells

PLoS ONE ◽

10.1371/journal.pone.0062660 ◽

2013 ◽

Vol 8 (5) ◽

pp. e62660 ◽

Cited By ~ 17

Author(s):

Ten-Tsao Wong ◽

Abraham Tesfamichael ◽

Paul Collodi

Keyword(s):

Stem Cells ◽

Germline Stem Cells ◽

Female Germline

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Effects of bisphenol A on ovarian follicular development and female germline stem cells

Archives of Toxicology ◽

10.1007/s00204-018-2167-2 ◽

2018 ◽

Vol 92 (4) ◽

pp. 1581-1591 ◽

Cited By ~ 12

Author(s):

Xiaoqin Zhu ◽

Geng G. Tian ◽

Baoli Yu ◽

Yanzhou Yang ◽

Ji Wu

Keyword(s):

Stem Cells ◽

Bisphenol A ◽

Follicular Development ◽

Germline Stem Cells ◽

Ovarian Follicular Development ◽

Female Germline

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The Controversy, Challenges, and Potential Benefits of Putative Female Germline Stem Cells Research in Mammals

Stem Cells International ◽

10.1155/2016/1728278 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Zezheng Pan ◽

Mengli Sun ◽

Xia Liang ◽

Jia Li ◽

Fangyue Zhou ◽

...

Keyword(s):

Stem Cells ◽

Germ Cell ◽

Germ Cells ◽

Mammalian Species ◽

Research Progress ◽

Germline Stem Cells ◽

Conventional View ◽

Proliferation And Differentiation ◽

Potential Benefits ◽

Female Germline

The conventional view is that female mammals lose their ability to generate new germ cells after birth. However, in recent years, researchers have successfully isolated and cultured a type of germ cell from postnatal ovaries in a variety of mammalian species that have the abilities of self-proliferation and differentiation into oocytes, and this finding indicates that putative germline stem cells maybe exist in the postnatal mammalian ovaries. Herein, we review the research history and discovery of putative female germline stem cells, the concept that putative germline stem cells exist in the postnatal mammalian ovary, and the research progress, challenge, and application of putative germline stem cells in recent years.

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Characteristics of Female Germline Stem Cells from Porcine Ovaries at Sexual Maturity

Cell Transplantation ◽

10.1177/0963689718784878 ◽

2018 ◽

Vol 27 (8) ◽

pp. 1195-1202 ◽

Cited By ~ 3

Author(s):

Lin Hou ◽

Jian Wang ◽

Xinyue Li ◽

Hu Wang ◽

Guishu Liu ◽

...

Keyword(s):

Stem Cells ◽

Sexual Maturity ◽

Germline Stem Cells ◽

Isolation And Purification ◽

Animal Biotechnology ◽

Regeneration Medicine ◽

Tissue Grafts ◽

Female Germline ◽

Mini Pigs ◽

Viable Model

Pigs share many anatomical and physiological features with humans, offering a unique and viable model for biomedical research. Although porcine female germline stem cells (FGSCs) were identified in the juvenile ovary, no reports described the isolation and purification of FGSCs from the pig at sexual maturity. Here, we isolated, purified, and cultured FGSCs from porcine ovaries at sexual maturity. Furthermore, we established and characterized the porcine FGSC (pFGSC) lines. In addition, we found that pFGSC lines could differentiate into oocytes when injection into tissue grafts, including human ovarian tissues. The results show that FGSCs exist in ovaries of Banna mini-pigs at juvenile and sexually maturity. These findings have implications in animal biotechnology applications and regeneration medicine.

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