Artificially produced gametes in mice, humans and other species

2021 ◽  
Vol 33 (2) ◽  
pp. 91
Author(s):  
Katsuhiko Hayashi ◽  
Cesare Galli ◽  
Sebastian Diecke ◽  
Thomas B. Hildebrandt
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Pluripotent Stem Cells ◽  
Mammalian Species ◽  
Cell Development ◽  
Current Status ◽  
Alternative Source ◽  
Germ Cell Development ◽  
Further Development

The production of gametes from pluripotent stem cells in culture, also known as invitro gametogenesis, will make an important contribution to reproductive biology and regenerative medicine, both as a unique tool for understanding germ cell development and as an alternative source of gametes for reproduction. Invitro gametogenesis was developed using mouse pluripotent stem cells but is increasingly being applied in other mammalian species, including humans. In principle, the entire process of germ cell development is nearly reconstitutable in culture using mouse pluripotent stem cells, although the fidelity of differentiation processes and the quality of resultant gametes remain to be refined. The methodology in the mouse system is only partially applicable to other species, and thus it must be optimised for each species. In this review, we update the current status of invitro gametogenesis in mice, humans and other animals, and discuss challenges for further development of this technology.

scholarly journals Stem cells, in vitro gametogenesis and male fertility

Reproduction ◽  
2017 ◽  
Vol 154 (6) ◽  
pp. F79-F91 ◽  
Author(s):  
Go Nagamatsu ◽  
Katsuhiko Hayashi
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Pluripotent Stem Cells ◽  
Cell Development ◽  
Biological Processes ◽  
Stem Cell Technology ◽  
Alternative Source ◽  
Germ Cell Development ◽  
Future Challenges

Reconstitution in culture of biological processes, such as differentiation and organization, is a key challenge in regenerative medicine, and one in which stem cell technology plays a central role. Pluripotent stem cells and spermatogonial stem cells are useful materials for reconstitution of germ cell development in vitro, as they are capable of differentiating into gametes. Reconstitution of germ cell development, termed in vitro gametogenesis, will provide an experimental platform for a better understanding of germ cell development, as well as an alternative source of gametes for reproduction, with the potential to cure infertility. Since germ cells are the cells for ‘the next generation’, both the culture system and its products must be carefully evaluated. In this issue, we summarize the progress in in vitro gametogenesis, most of which has been made using mouse models, as well as the future challenges in this field.

006. HUMAN GERM CELL FORMATION AND DIFFERENTIATION FROM PLURIPOTENT STEM CELLS

2010 ◽  
Vol 22 (9) ◽  
pp. 5
Author(s):  
R. A. ReijoPiera
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Germ Cells ◽  
Pluripotent Stem Cells ◽  
Rna Binding ◽  
Cell Formation ◽  
Cell Development ◽  
Model Organisms ◽  
Germ Cell Development ◽  
Germ Cell Formation

Human embryo development begins with the fusion of egg and sperm, followed by reprogramming of the DNA, a series of cell divisions and activation of the embryo’s genome. As development continues, the germ cells (egg and sperm) must be set aside from other cell types. A major cause of infertility in men and women is quantitative and qualitative defects in human germ cell (oocyte and sperm) development. Yet, it has been difficult to study human germ cell development, especially features that are unique relative to model organisms. We have developed a system to differentiate human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) to germ cells and to quantitate and isolate primordial germ cells (PGCs) derived from both XX- and XY-bearing hESCs and iPSCs. This allowed silencing and overexpression of genes that encode germ cell-specific cytoplasmic RNA-binding proteins (not transcription factors) and resulted in the modulation of human male and female germ cell formation and developmental progression. We observed that human DAZL (Deleted in AZoospermia-Like) functions in female and male PGC formation and maintenance, whereas closely-related family members, BOULE and DAZ, promote entry into meiosis and development of haploid gametes with sperm-specific methylation patterns at imprinted loci in the male. We also conducted critical proof-of-concept studies in mice that showed that phenotypes observed in germ cell development in vitro from wildtype, heterozygous, and Dazl–/– mutation-carrying mouse ESCs (mESCs) mirrored the phenotypes that were observed in vivo. Furthermore, transplantation of XX mESC-derived oocytes resulted in recruitment of somatic cells to form follicles. These studies comprised the first direct experimental analysis of the genetics of human germ cell development and set the stage for extensive exploration of complex genetic variants linked to infertility. Results are significant to the generation of gametes for developmental genetic studies and potential clinical applications.

Induction of the germ cell fate from pluripotent stem cells in cynomolgus monkeys†

2019 ◽  
Vol 102 (3) ◽  
pp. 620-638 ◽  
Author(s):  
Yoshitake Sakai ◽  
Tomonori Nakamura ◽  
Ikuhiro Okamoto ◽  
Sayuri Gyobu-Motani ◽  
Hiroshi Ohta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Primordial Germ Cell ◽  
Embryonic Stem ◽  
Cell Development ◽  
Cynomolgus Monkeys ◽  
Germ Cell Development

Abstract In vitro reconstitution of germ-cell development from pluripotent stem cells (PSCs) has created key opportunities to explore the fundamental mechanisms underlying germ-cell development, particularly in mice and humans. Importantly, such investigations have clarified critical species differences in the mechanisms regulating mouse and human germ-cell development, highlighting the necessity of establishing an in vitro germ-cell development system in other mammals, such as non-human primates. Here, we show that multiple lines of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in cynomolgus monkeys (Macaca fascicularis; cy) can be maintained stably in an undifferentiated state under a defined condition with an inhibitor for WNT signaling, and such PSCs are induced efficiently into primordial germ cell-like cells (PGCLCs) bearing a transcriptome similar to early cyPGCs. Interestingly, the induction kinetics of cyPGCLCs from cyPSCs is faster than that of human (h) PGCLCs from hPSCs, and while the transcriptome dynamics during cyPGCLC induction is relatively similar to that during hPGCLC induction, it is substantially divergent from that during mouse (m) PGCLC induction. Our findings delineate common as well as species-specific traits for PGC specification, creating a foundation for parallel investigations into the mechanism for germ-cell development in mice, monkeys, and humans.

In vitro reconstitution of the whole male germ-cell development from mouse pluripotent stem cells

2021 ◽  
Author(s):  
Yukiko Ishikura ◽  
Hiroshi Ohta ◽  
Takuya Sato ◽  
Yusuke Murase ◽  
Yukihiro Yabuta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Pluripotent Stem Cells ◽  
Cell Development ◽  
Male Germ Cell ◽  
Germ Cell Development ◽  
In Vitro Reconstitution

Status of human germ cell differentiation from pluripotent stem cells

2013 ◽  
Vol 25 (2) ◽  
pp. 396 ◽  
Author(s):  
Renee A. Reijo Pera
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Germ Cells ◽  
Pluripotent Stem Cells ◽  
Clinical Applications ◽  
Current Status ◽  
Potential Utility ◽  
Germ Cell Differentiation ◽  
Infertile Couples

Historically, the quality of life of infertile couples has been greatly diminished by the loss of opportunity to conceive. However, beginning with the advent of IVF in the late 1970s, novel clinical interventions have greatly changed the outlook for those with severe forms of infertility. Yet, in cases in which the quality and quantity of germ cells are most compromised, there are few options. In the present paper, the current status of germ cell development from stem cells is reviewed in light of potential utility for basic science and clinical applications.

scholarly journals In Vitro Modeling of Human Germ Cell Development Using Pluripotent Stem Cells

2018 ◽  
Vol 10 (2) ◽  
pp. 509-523 ◽  
Author(s):  
Yuncheng Zhao ◽  
Shicheng Ye ◽  
Dongli Liang ◽  
Pengxiang Wang ◽  
Jing Fu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Pluripotent Stem Cells ◽  
Cell Development ◽  
In Vitro Modeling ◽  
Germ Cell Development

scholarly journals Survival Motor Neuron Protein Participates in Mouse Germ Cell Development and Spermatogonium Maintenance

2020 ◽  
Vol 21 (3) ◽  
pp. 794 ◽  
Author(s):  
Wei-Fang Chang ◽  
Jie Xu ◽  
Tzu-Ying Lin ◽  
Jing Hsu ◽  
Hsiu-Mei Hsieh-Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Motor Neuron ◽  
Cell Biology ◽  
Critical Role ◽  
Embryonic Stem ◽  
Cell Development ◽  
Survival Motor Neuron ◽  
Specific Marker ◽  
Germ Cell Development

The defective human survival motor neuron 1 (SMN1) gene leads to spinal muscular atrophy (SMA), the most common genetic cause of infant mortality. We previously reported that loss of SMN results in rapid differentiation of Drosophila germline stem cells and mouse embryonic stem cells (ESCs), indicating that SMN also plays important roles in germ cell development and stem cell biology. Here, we show that in healthy mice, SMN is highly expressed in the gonadal tissues, prepubertal spermatogonia, and adult spermatocytes, whereas low SMN expression is found in differentiated spermatid and sperm. In SMA-like mice, the growth of testis tissues is retarded, accompanied with gamete development abnormalities and loss of the spermatogonia-specific marker. Consistently, knockdown of Smn1 in spermatogonial stem cells (SSCs) leads to a compromised regeneration capacity in vitro and in vivo in transplantation experiments. In SMA-like mice, apoptosis and accumulation of the R-loop structure were significantly elevated, indicating that SMN plays a critical role in the survival of male germ cells. The present work demonstrates that SMN, in addition to its critical roles in neuronal development, participates in mouse germ cell and spermatogonium maintenance.

The DAZ gene family and human germ cell development from embryonic stem cells

2009 ◽  
pp. 323-350
Author(s):  
Mark S. Fox ◽  
Renee A. Reijo Pera ◽  
Amander T. Clark
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Germ Cell ◽  
Gene Family ◽  
Embryonic Stem ◽  
Cell Development ◽  
Germ Cell Development ◽  
I Gene

Embryonic Stem Cells: A Novel Attractive Research Tool for Germ Cell Development

2012 ◽  
Vol 29 (1) ◽  
pp. 11-16
Author(s):  
Naoto Fukunaga ◽  
Takeshi Teramura ◽  
Yoshihiko Hosoi
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Germ Cell ◽  
Embryonic Stem ◽  
Cell Development ◽  
Research Tool ◽  
Germ Cell Development

scholarly journals Somatic regulation of female germ cell regeneration and development in planarians

2021 ◽  
Author(s):  
Umair W. Khan ◽  
Phillip A Newmark
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Pluripotent Stem Cells ◽  
Cell Development ◽  
Molecular Signatures ◽  
Germ Cell Development ◽  
Ovarian Cells ◽  
Planarian Regeneration ◽  
Female Germ Cell ◽  
Oocyte Differentiation

Female germ cells develop into oocytes, with the capacity for totipotency. In most animals, these remarkable cells are specified during development and cannot be regenerated. By contrast, planarians, known for their regenerative prowess, can regenerate germ cells. To uncover mechanisms required for female germ cell development and regeneration, we generated gonad-specific transcriptomes and identified genes whose expression defines progressive stages of female germ cell development. Strikingly, early female germ cells share molecular signatures with the pluripotent stem cells driving planarian regeneration. We uncovered spatial heterogeneity within somatic ovarian cells and found that a regionally enriched FoxL homolog is required for oocyte differentiation, but not specification, suggestive of functionally distinct somatic compartments. Unexpectedly, a neurotransmitter-biosynthetic enzyme, AADC, is also expressed in somatic gonadal cells, and plays opposing roles in female and male germ cell development. Thus, somatic gonadal cells deploy conserved factors to regulate germ cell development and regeneration in planarians.

Sign in / Sign up

Export Citation Format

Share Document