scholarly journals Offspring production of ovarian organoids derived from spermatogonial stem cells by chromatin reorganization

2019 ◽  
Author(s):  
Huacheng Luo ◽  
Xiaoyong Li ◽  
Geng G. Tian ◽  
Dali Li ◽  
Changliang Hou ◽  
...  
Keyword(s):  
Stem Cells ◽  
3D Cell Culture ◽  
Spermatogonial Stem Cells ◽  
Germline Stem Cells ◽  
Chromosome Conformation ◽  
Offspring Production ◽  
Whole Exome ◽  
Female Germline ◽  
Chromatin Reorganization

AbstractFate determination of germline stem cells remains poorly understood at the chromatin structure level1,2. Here, we demonstrate successful production of offspring from oocytes transdifferentiated from mouse spermatogonial stem cells (SSCs) with tracking of transplanted SSCs in vivo, single cell whole exome sequencing, and in 3D cell culture reconstitution of the process of oogenesis derived from SSCs. Furthermore, we demonstrate direct induction of germline stem cells (iGSCs) differentiated into functional oocytes by transduction of H19, Stella, and Zfp57 and inactivation of Plzf in SSCs after screening with ovarian organoids. Using high throughput chromosome conformation, we uncovered extensive chromatin reorganization during SSC conversion into iGSCs, which was highly similar to female germline stem cells. We observed that although topologically associating domains were stable during SSC conversion, chromatin interactions changed in a striking manner, altering 35% of inactive and active chromosomal compartments throughout the genome. These findings have important implications in various areas including mammalian gametogenesis, genetic and epigenetic reprogramming, biotechnology, and medicine.

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.

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 The asymmetric segregation of damaged proteins is stem cell–type dependent

2013 ◽  
Vol 201 (4) ◽  
pp. 523-530 ◽  
Author(s):  
Mary Rose Bufalino ◽  
Brian DeVeale ◽  
Derek van der Kooy
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Intestinal Stem Cell ◽  
Germline Stem Cells ◽  
Cell Type ◽  
Chronological Life Span ◽  
A Cell ◽  
Female Germline

Asymmetric segregation of damaged proteins (DPs) during mitosis has been linked in yeast and bacteria to the protection of one cell from aging. Recent evidence suggests that stem cells may use a similar mechanism; however, to date there is no in vivo evidence demonstrating this effect in healthy adult stem cells. We report that stem cells in larval (neuroblast) and adult (female germline and intestinal stem cell) Drosophila melanogaster asymmetrically segregate DPs, such as proteins with the difficult-to-degrade and age-associated 2,4-hydroxynonenal (HNE) modification. Surprisingly, of the cells analyzed only the intestinal stem cell protects itself by segregating HNE to differentiating progeny, whereas the neuroblast and germline stem cells retain HNE during division. This led us to suggest that chronological life span, and not cell type, determines the amount of DPs a cell receives during division. Furthermore, we reveal a role for both niche-dependent and -independent mechanisms of asymmetric DP division.

scholarly journals Tracing and Characterizing the Development of Transplanted Female Germline Stem Cells In Vivo

2017 ◽  
Vol 25 (6) ◽  
pp. 1408-1419 ◽  
Author(s):  
Changqing Wu ◽  
Bo Xu ◽  
Xiaoyong Li ◽  
Wenzhi Ma ◽  
Ping Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germline Stem Cells ◽  
Female Germline

scholarly journals Improvement in Isolation and Identification of Mouse Oogonial Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Zhiyong Lu ◽  
Meng Wu ◽  
Jinjin Zhang ◽  
Jiaqiang Xiong ◽  
Jing Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Umbilical Cord ◽  
Germline Stem Cells ◽  
Feeder Cells ◽  
Isolation And Identification ◽  
Tissue Sections ◽  
Female Germline ◽  
Magnetic Activated Cell Sorting

Female germline stem cells (FGSCs) or oogonial stem cells (OSCs) have the capacity to generate newborn oocytes and thus open a new door to fight ovarian aging and female infertility. However, the production and identification of OSCs are difficult for investigators. Rare amount of these cells in the ovary results in the failure of the acquisition of OSCs. Furthermore, the oocyte formation by OSCs in vivo was usually confirmed using tissue sections by immunofluorescence or immunohistochemistry in previous studies. STO or MEF feeder cells are derived from mouse, not human. In our study, we modified the protocol. The cells were digested from ovaries and cultured for 2-3 days and then were purified by magnetic-activated cell sorting (MACS). The ovaries and fetus of mice injected with EGFP-positive OSCs were prepared and put on the slides to directly visualize oocyte and progeny formation under microscope. Additionally, the human umbilical cord mesenchymal stem cells (hUC-MSCs) were also used as feeder cells to support the proliferation of OSCs. The results showed that all the modified procedures can significantly improve and facilitate the generation and characterization of OSCs, and hUC-MSCs as feeder will be useful for isolation and proliferation of human OSCs avoiding contamination from mouse.

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

2012 ◽  
Vol 45 (4) ◽  
pp. 287-298 ◽  
Author(s):  
Y. Hu ◽  
Y. Bai ◽  
Z. Chu ◽  
J. Wang ◽  
L. Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germline Stem Cells ◽  
Mouse Ovary ◽  
Female Germline ◽  
Gsk3 Inhibitor
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