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

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
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.

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

2010 ◽  
Vol 17 (4) ◽  
pp. 498-505 ◽  
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.

scholarly journals Enrichment of Female Germline Stem Cells from Mouse Ovaries Using the Differential Adhesion Method

2018 ◽  
Vol 46 (5) ◽  
pp. 2114-2126 ◽  
Author(s):  
Meng Wu ◽  
Jiaqiang Xiong ◽  
Lingwei Ma ◽  
Zhiyong Lu ◽  
Xian Qin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Akt Pathway ◽  
Germline Stem Cells ◽  
Self Renewal ◽  
Differential Adhesion ◽  
Proliferation And Differentiation ◽  
Phosphoinositide 3 Kinase ◽  
Female Germline

Background/Aims: The isolation and establishment of female germline stem cells (FGSCs) is controversial because of questions regarding the reliability and stability of the isolation method using antibody targeting mouse vasa homologue (MVH), and the molecular mechanism of FGSCs self-renewal remains unclear. Thus, there needs to be a simple and reliable method for sorting FGSCs to study them. Methods: We applied the differential adhesion method to enrich FGSCs (DA-FGSCs) from mouse ovaries. Through four rounds of purification and 7-9 subsequent passages, DA-FGSC lines were established. In addition, we assessed the role of the phosphoinositide-3 kinase (PI3K)-AKT pathway in regulating FGSC self-renewal. Results: The obtained DA-FGSCs spontaneously differentiated into oocyte-like cells in vitro and formed functional eggs in vivo that were fertilized and produced healthy offspring. AKT was rapidly phosphorylated when the proliferation rate of FGSCs increased after 10 passages, and the addition of a chemical PI3K inhibitor prevented FGSCs self-renewal. Furthermore, over-expression of AKT-induced proliferation and differentiation of FGSCs, c-Myc, Oct-4 and Gdf-9 levels were increased. Conclusions: The differential adhesion method provides a more feasible approach and is an easier procedure to establish FGSC lines than traditional methods. The AKT pathway plays an important role in regulation of the proliferation and maintenance of FGSCs. These findings could help promote stem cell studies and provide a better understanding of causes of ovarian infertility, thereby providing potential treatments for infertility.

scholarly journals Germline Sex Determination regulates sex-specific signaling between germline stem cells and their niche

2021 ◽  
Author(s):  
Pradeep Kumar Bhaskar ◽  
Sheryl Southard ◽  
Kelly Baxter ◽  
Mark Van Doren
Keyword(s):  
Stem Cells ◽  
Sex Determination ◽  
Sexual Identity ◽  
Germ Cells ◽  
Sex Chromosome ◽  
Germline Stem Cells ◽  
Somatic Gonad ◽  
Stat Signaling ◽  
Female Germline ◽  
Germline Sex Determination

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.

scholarly journals Offspring production of haploid spermatid-like cells derived from mouse female germline stem cells with chromatin condensation

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaopeng Hu ◽  
Hu Wang ◽  
Geng. G. Tian ◽  
Changliang Hou ◽  
Bo Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Y Chromosome ◽  
Germ Cells ◽  
Chromatin Condensation ◽  
Germline Stem Cells ◽  
Chromosome Conformation ◽  
Female Germline

Abstract Background During male meiosis, the Y chromosome can form perfect pairing with the X chromosome. However, it is unclear whether mammalian Female germline stem cells (FGSCs) without a Y chromosome can transdifferentiate into functional haploid spermatid-like cells (SLCs). Results We found that spermatogenesis was restarted by transplanting FGSCs into Kitw/wv mutant testes. Complete meiosis and formation of SLCs was induced in vitro by testicular cells of Kitw/wv mutant mice, cytokines and retinoic acid. Healthy offspring were produced by sperm and SLCs derived from the in vivo and in vitro transdifferentiation of FGSCs, respectively. Furthermore, high-throughput chromosome conformation capture sequencing(Hi-C-seq) and “bivalent” (H3K4me3-H3K27me3) micro chromatin immunoprecipitation sequencing (μChIP-seq) experiments showed that stimulated by retinoic acid gene 8 (STRA8)/protamine 1 (PRM1)-positive transdifferentiated germ cells (tGCs) and male germ cells (mGCs) display similar chromatin dynamics and chromatin condensation during in vitro spermatogenesis. Conclusion This study demonstrates that sperm can be produced from FGSCs without a Y chromosome. This suggests a strategy for dairy cattle breeding to produce only female offspring with a high-quality genetic background.

A role for the Drosophila bag-of-marbles protein in the differentiation of cystoblasts from germline stem cells

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2937-2947 ◽  
Author(s):  
D. McKearin ◽  
B. Ohlstein
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Germ Cell ◽  
Germ Cells ◽  
Germline Stem Cell ◽  
Cytoplasmic Protein ◽  
Germline Stem Cells ◽  
Bag Of Marbles

Cell differentiation commonly dictates a change in the cell cycle of mitotic daughters. Previous investigations have suggested that the Drosophila bag of marbles (bam) gene is required for the differentiation of germline stem cell daughters (cystoblasts) from the mother stem cells, perhaps by altering the cell cycle. In this paper, we report the preparation of antibodies to the Bam protein and the use of those reagents to investigate how Bam is required for germ cell development. We find that Bam exists as both a fusome component and as cytoplasmic protein and that cytoplasmic and fusome Bam might have separable activities. We also show that bam mutant germ cells are blocked in differentiation and are trapped as mitotically active cells like stem cells. A model for how Bam might regulate cystocyte differentiation is presented.

scholarly journals Male germline stem cells in non-human primates

2017 ◽  
Vol 4 (2) ◽  
pp. 173-184 ◽  
Author(s):  
Swati Sharma ◽  
Joana M. D. Portela ◽  
Daniel Langenstroth-Röwer ◽  
Joachim Wistuba ◽  
Nina Neuhaus ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Germ Cells ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Regulatory Mechanisms ◽  
Primate Species ◽  
Germline Stem Cells ◽  
Germline Development ◽  
Human Primate

Abstract. Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs). These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys) are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs) are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28) during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of human fertility preservation strategies.

scholarly journals Krüppel-like factor 4 is required for development and regeneration of germline and yolk cells from somatic stem cells in planarians

2021 ◽  
Author(s):  
Melanie Issigonis ◽  
Akshada Redkar ◽  
Tania Rozario ◽  
Umair Khan ◽  
Rosa Mejia-Sanchez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Germ Cells ◽  
System Development ◽  
Primordial Germ Cells ◽  
Reproductive Organs ◽  
Germline Stem Cells ◽  
Yolk Cell ◽  
Evolutionary Innovation ◽  
Parasitic Flatworm

Sexually reproducing animals segregate their germline from their soma. In addition to gamete-producing gonads, planarian and parasitic flatworm reproduction relies on yolk-cell-generating accessory reproductive organs (vitellaria) supporting development of yolkless oocytes. Despite the importance of vitellaria for flatworm reproduction (and parasite transmission), little is known about this unique evolutionary innovation. Here we examine reproductive system development in the planarian Schmidtea mediterranea, in which pluripotent stem cells generate both somatic and germ cell lineages. We show that a homolog of the pluripotency factor Klf4 is expressed in primordial germ cells, presumptive germline stem cells, and yolk-cell progenitors. klf4 knockdown animals fail to specify or maintain germ cells; surprisingly, they also fail to maintain yolk cells. We find that yolk cells display germ-cell-like attributes and that vitellaria are structurally analogous to gonads. In addition to identifying a new proliferative cell population in planarians (yolk cell progenitors) and defining its niche, our work provides evidence supporting the hypothesis that flatworm germ cells and yolk cells share a common evolutionary origin.

scholarly journals Defining the expression of piRNA and transposable elements in Drosophila ovarian germline stem cells and somatic support cells

2019 ◽  
Vol 2 (5) ◽  
pp. e201800211 ◽  
Author(s):  
Benjamin Story ◽  
Xing Ma ◽  
Kazue Ishihara ◽  
Hua Li ◽  
Kathryn Hall ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transposable Elements ◽  
Germ Cell ◽  
Germ Cells ◽  
Genome Stability ◽  
Cell Function ◽  
Germline Stem Cells ◽  
Sequencing Data ◽  
Rich Information ◽  
The Rich

Piwi-interacting RNAs (piRNAs) are important for repressing transposable elements (TEs) and modulating gene expression in germ cells, thereby maintaining genome stability and germ cell function. Although they are also important for maintaining germline stem cells (GSCs) in the Drosophila ovary by repressing TEs and preventing DNA damage, piRNA expression has not been investigated in GSCs or their early progeny. Here, we show that the canonical piRNA clusters are more active in GSCs and their early progeny than late germ cells and also identify more than 3,000 new piRNA clusters from deep sequencing data. The increase in piRNAs in GSCs and early progeny can be attributed to both canonical and newly identified piRNA clusters. As expected, piRNA clusters in GSCs, but not those in somatic support cells (SCs), exhibit ping-pong signatures. Surprisingly, GSCs and early progeny express more TE transcripts than late germ cells, suggesting that the increase in piRNA levels may be related to the higher levels of TE transcripts in GSCs and early progeny. GSCs also have higher piRNA levels and lower TE levels than SCs. Furthermore, the 3′ UTRs of 171 mRNA transcripts may produce sense, antisense, or dual-stranded piRNAs. Finally, we show that alternative promoter usage and splicing are frequently used to modulate gene function in GSCs and SCs. Overall, this study has provided important insight into piRNA production and TE repression in GSCs and SCs. The rich information provided by this study will be a beneficial resource to the fields of piRNA biology and germ cell development.

The somatic sex determines the requirement for ovarian tumor gene activity in the proliferation of the Drosophila germline

Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 579-587 ◽  
Author(s):  
R.N. Nagoshi ◽  
J.S. Patton ◽  
E. Bae ◽  
P.K. Geyer
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Rna Splicing ◽  
Ovarian Tumor ◽  
Specific Gene ◽  
Genetic Components ◽  
Somatic Gonad ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Female Germline

Gametogenesis in Drosophila requires sex-specific interactions between the soma and germline to control germ cell viability, proliferation, and differentiation. To determine what genetic components are involved in this interaction, we examined whether changes in the sexual identity of the soma affected the function of the ovarian tumor (otu) and ovo genes. These genes are required cell autonomously in the female germline for germ cell proliferation and differentiation. Mutations in otu and ovo cause a range of ovarian defects, including agametic ovaries and tumorous egg cysts, but do not affect spermatogenesis. We demonstrate that XY germ cells do not require otu when developing in testes, but become dependent on otu function for proliferation when placed in an ovary. This soma-induced requirement can be satisfied by the induced expression of the 98 × 10(3) M(r) OTU product, one of two isoforms produced by differential RNA splicing. These results indicate that the female somatic gonad can induce XY germ cells to become ‘female-like’ because they require an oogenesis-specific gene. In contrast, the requirement for ovo is dependent on a cell autonomous signal derived from the X:A ratio. We propose that differential regulation of the otu and ovo genes provides a mechanism for the female germline to incorporate both somatic and cell autonomous inputs required for oogenesis.

Ectopic expression of the Drosophila Bam protein eliminates oogenic germline stem cells

Development ◽  
1997 ◽  
Vol 124 (18) ◽  
pp. 3651-3662 ◽  
Author(s):  
B. Ohlstein ◽  
D. McKearin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Germ Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Ectopic Expression ◽  
Cell Lineage ◽  
Limiting Factor ◽  
Germline Stem Cells ◽  
Stem Cell Divisions

The Drosophila germ-cell lineage has emerged as a remarkable system for identifying genes required for changes in cell fate from stem cells into more specialized cells. Previous work indicates that bam expression is necessary for cystoblast differentiation; bam mutant germ cells fail to differentiate, but instead proliferate like stem cells. This paper reports that ectopic expression of bam is sufficient to extinguish stem cell divisions. Heat-induced bam+ expression specifically eliminated oogenic stem cells while somatic stem cell populations were not affected. Together with previous studies of the timing of bam mRNA and protein expression and the state of arrest in bam mutant cells, these data implicate Bam as a direct regulator of the switch from stem cell to cystoblast. Surprisingly, ectopic bam+ had no deleterious consequences for male germline cells suggesting that Bam may regulate somewhat different steps of germ-cell development in oogenesis and spermatogenesis. We discuss a model for how bam+ could direct differentiation based on our data (McKearin and Ohlstein, 1995) that Bam protein is essential to assemble part of the germ-cell-specific organelle, the fusome. We propose that fusome biogenesis is an obligate step for cystoblast cell fate and that Bam is the limiting factor for fusome maturation in female germ cells.

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