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

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

Cell & Bioscience ◽

10.1186/s13578-021-00697-z ◽

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.

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Sex Determination Signals Control ovo-B Transcription in Drosophila melanogaster Germ Cells

Genetics ◽

10.1093/genetics/160.2.537 ◽

2002 ◽

Vol 160 (2) ◽

pp. 537-545

Author(s):

Justen Andrews ◽

Brian Oliver

Keyword(s):

Transcription Factor ◽

Drosophila Melanogaster ◽

Genetic Analysis ◽

Sex Determination ◽

Sexual Identity ◽

Germ Cells ◽

Female Germline ◽

Chromosome Karyotype ◽

Inductive Signals

Abstract Nonautonomous inductive signals from the soma and autonomous signals due to a 2X karyotype determine the sex of Drosophila melanogaster germ cells. These two signals have partially overlapping influences on downstream sex determination genes. The upstream OVO-B transcription factor is required for the viability of 2X germ cells, regardless of sexual identity, and for female germline sexual identity. The influence of inductive and autonomous signals on ovo expression has been controversial. We show that ovo-B is strongly expressed in the 2X germ cells in either a male or a female soma. This indicates that a 2X karyotype controls ovo-B expression in the absence of inductive signals from the female soma. However, we also show that female inductive signals positively regulate ovo-B transcription in the 1X germ cells that do not require ovo-B function. Genetic analysis clearly indicates that inductive signals from the soma are not required for ovo-B function in 2X germ cells. Thus, while somatic inductive signals and chromosome karyotype have overlapping regulatory influences, a 2X karyotype is a critical germline autonomous determinant of ovo-B function in the germline.

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Germline Sex Determination Regulates Sex-Specific Signaling Between Germline Stem Cells and Their Niche

SSRN Electronic Journal ◽

10.2139/ssrn.3862016 ◽

2021 ◽

Author(s):

Pradeep Kumar Bhaskar ◽

Sheryl Southard ◽

Kelley Baxter ◽

Mark Van Doren

Keyword(s):

Stem Cells ◽

Sex Determination ◽

Germline Stem Cells ◽

Germline Sex Determination

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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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