scholarly journals Differential repression of Otx2 underlies the capacity of NANOG and ESRRB to induce germline entry

2021 ◽  
Author(s):  
Matus Vojtek ◽  
Jingchao Zhang ◽  
Juanjuan Sun ◽  
Man Zhang ◽  
Ian Chambers
Keyword(s):  
Transcription Factor ◽  
Germ Cells ◽  
Target Gene ◽  
Primordial Germ Cells ◽  
The Core ◽  
Underlying Mechanisms ◽  
Post Implantation ◽  
Embryonic Ectoderm

Primordial germ cells (PGCs) are induced in the embryo by signals, including BMP emanating from extra-embryonic ectoderm, that act on cells in the post-implantation epiblast. PGC development can be recapitulated in vitro through the exposure of epiblast-like cells (EpiLCs) to appropriate cytokines, resulting in differentiation into PGC-like cells (PGCLCs). Interestingly, the requirement for cytokines to induce PGCLCs can be bypassed by enforced expression of the transcription factor (TF) NANOG. However, the underlying mechanisms are not fully elucidated. Here, we show that Otx2 downregulation is essential to enable NANOG to induce PGCLC formation. Moreover, while previous work has shown that the direct NANOG target gene Esrrb can substitute for several functions of NANOG, enforced expression of ESRRB cannot promote PGCLC specification from EpiLCs. This appears to be due to differential downregulation of Otx2 by NANOG and ESRRB, since induction of ESRRB in Otx2+/- EpiLCs activates expression of the core PGC TFs, Blimp1, Prdm14 and Ap2γ and emergence of PGCLCs. This study illuminates the interplay of TFs occurring at the earliest stages of PGC specification from a state of competence.

scholarly journals Specification of the germline by Nanos-dependent down-regulation of the somatic synMuvB transcription factor LIN-15B

2017 ◽  
Author(s):  
Chih-Yung S. Lee ◽  
Tu Lu ◽  
Geraldine Seydoux
Keyword(s):  
Transcription Factor ◽  
Germ Cells ◽  
Rna Binding ◽  
Primordial Germ Cells ◽  
Somatic Cells ◽  
Rna Binding Protein ◽  
Dependent Manner ◽  
Embryonic Cells ◽  
C Elegans ◽  
Underlying Mechanisms

AbstractThe Nanos RNA-binding protein has been implicated in the specification of primordial germ cells (PGCs) in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of PGCs lacking the nanos homologues nos-1 and nos-2 iC. elegans. nos-1nos-2 PGCs fail to silence hundreds of genes normally expressed in oocytes and somatic cells, a phenotype reminiscent of PGCs lacking the repressive PRC2 complex. The nos-1nos-2 phenotype depends on LIN-15B, a broadly expressed synMuvB class transcription factor known to antagonize PRC2 activity in somatic cells. LIN-15B is maternally-inherited by all embryonic cells and is down-regulated specifically in PGCs in a nos-1nos-2-dependent manner. Consistent with LIN-15B being a critical target of Nanos regulation, inactivation of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These studies demonstrate a central role for Nanos in reprogramming the transcriptome of PGCs away from an oocyte/somatic fate by down-regulating an antagonist of PRC2 activity.

scholarly journals Formative pluripotent stem cells show features of epiblast cells poised for gastrulation

Cell Research ◽  
2021 ◽  
Author(s):  
Xiaoxiao Wang ◽  
Yunlong Xiang ◽  
Yang Yu ◽  
Ran Wang ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cells ◽  
Pluripotent Stem Cells ◽  
Primordial Germ Cells ◽  
Embryonic Stem ◽  
Large Set ◽  
Mouse Escs ◽  
Epiblast Stem Cells ◽  
Early Gastrula

AbstractThe pluripotency of mammalian early and late epiblast could be recapitulated by naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), respectively. However, these two states of pluripotency may not be sufficient to reflect the full complexity and developmental potency of the epiblast during mammalian early development. Here we report the establishment of self-renewing formative pluripotent stem cells (fPSCs) which manifest features of epiblast cells poised for gastrulation. fPSCs can be established from different mouse ESCs, pre-/early-gastrula epiblasts and induced PSCs. Similar to pre-/early-gastrula epiblasts, fPSCs show the transcriptomic features of formative pluripotency, which are distinct from naïve ESCs and primed EpiSCs. fPSCs show the unique epigenetic states of E6.5 epiblast, including the super-bivalency of a large set of developmental genes. Just like epiblast cells immediately before gastrulation, fPSCs can efficiently differentiate into three germ layers and primordial germ cells (PGCs) in vitro. Thus, fPSCs highlight the feasibility of using PSCs to explore the development of mammalian epiblast.

Effects of apoptosis inhibitors on survival of porcine primordial germ cells in vitro

1999 ◽  
Vol 51 (1) ◽  
pp. 208 ◽  
Author(s):  
C-K Lee ◽  
R Weaks ◽  
J.A Piedrahita
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells

scholarly journals Differentiation of Mouse Primordial Germ Cells into Functional Oocytes In Vitro

2017 ◽  
Vol 45 (7) ◽  
pp. 1608-1619 ◽  
Author(s):  
Kanako Morohaku ◽  
Yuji Hirao ◽  
Yayoi Obata
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells

scholarly journals Ligand–Receptor Interactions Elucidate Sex-Specific Pathways in the Trajectory From Primordial Germ Cells to Gonia During Human Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Arend W. Overeem ◽  
Yolanda W. Chang ◽  
Jeroen Spruit ◽  
Celine M. Roelse ◽  
Susana M. Chuva De Sousa Lopes
Keyword(s):  
Germ Cell ◽  
Signaling Pathways ◽  
Germ Cells ◽  
Tyrosine Kinases ◽  
Intracellular Localization ◽  
Primordial Germ Cells ◽  
Cell Lineage ◽  
Systematic Analysis ◽  
Receptor Interactions

The human germ cell lineage originates from primordial germ cells (PGCs), which are specified at approximately the third week of development. Our understanding of the signaling pathways that control this event has significantly increased in recent years and that has enabled the generation of PGC-like cells (PGCLCs) from pluripotent stem cells in vitro. However, the signaling pathways that drive the transition of PGCs into gonia (prospermatogonia in males or premeiotic oogonia in females) remain unclear, and we are presently unable to mimic this step in vitro in the absence of gonadal tissue. Therefore, we have analyzed single-cell transcriptomics data of human fetal gonads to map the molecular interactions during the sex-specific transition from PGCs to gonia. The CellPhoneDB algorithm was used to identify significant ligand–receptor interactions between germ cells and their sex-specific neighboring gonadal somatic cells, focusing on four major signaling pathways WNT, NOTCH, TGFβ/BMP, and receptor tyrosine kinases (RTK). Subsequently, the expression and intracellular localization of key effectors for these pathways were validated in human fetal gonads by immunostaining. This approach provided a systematic analysis of the signaling environment in developing human gonads and revealed sex-specific signaling pathways during human premeiotic germ cell development. This work serves as a foundation to understand the transition from PGCs to premeiotic oogonia or prospermatogonia and identifies sex-specific signaling pathways that are of interest in the step-by-step reconstitution of human gametogenesis in vitro.

scholarly journals Protocol for controlled modeling of human epiblast and amnion development using stem cells

2019 ◽  
Author(s):  
Yi Zheng ◽  
Jianping Fu
Keyword(s):  
Stem Cells ◽  
Primordial Germ Cells ◽  
Primitive Streak ◽  
Human Embryos ◽  
Vitro Fertilization ◽  
Human Embryology ◽  
Post Implantation ◽  
Advance Knowledge ◽  
Early Human

Abstract Due to the inaccessibility of post-implantation human embryos and the restriction on in-vitro fertilization (IVF) embryos cultured beyond 14 days, the knowledge of early post-implantation human embryogenesis remains extremely limited. Recently, we have developed a microfluidic in-vitro platform, based on human pluripotent stem cells (hPSCs), which is capable of recapitulating several key developmental landmarks of early human post-implantation embryonic development, including lumenogenesis of the epiblast (EPI), amniogenesis, and specification of primordial germ cells (PGCs) and of primitive streak (PS) cells. Given its controllability and reproducibility, the microfluidic platform provides a powerful experimental platform to advance knowledge of human embryology and reproduction. This protocol describes the preparation of the microfluidic device and its implementation for modeling human post-implantation epiblast and amnion development using hPSCs.

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