Efficient Induction of Pluripotency in Primordial Germ Cells by Dual Inhibition of TGF-β and ERK Signaling Pathways

2014 ◽  
Vol 23 (10) ◽  
pp. 1050-1061 ◽  
Author(s):  
Farnoosh Attari ◽  
Houri Sepehri ◽  
Hassan Ansari ◽  
Seyedeh-Nafiseh Hassani ◽  
Fereshteh Esfandiari ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Erk Signaling ◽  
Efficient Induction ◽  
Dual Inhibition

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 Chemoattractant action and molecular signaling pathways of Kit ligand on mouse primordial germ cells

2007 ◽  
Vol 306 (2) ◽  
pp. 572-583 ◽  
Author(s):  
Donatella Farini ◽  
Gina La Sala ◽  
Marianna Tedesco ◽  
Massimo De Felici
Keyword(s):  
Signaling Pathways ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Molecular Signaling ◽  
Kit Ligand ◽  
Molecular Signaling Pathways

scholarly journals Azasteroid Alkylators as Dual Inhibitors of AKT and ERK Signaling for the Treatment of Ovarian Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1263 ◽  
Author(s):  
Panagiotis Dalezis ◽  
Eleni Geromichalou ◽  
Aikaterini Polonifi ◽  
Sofia Sagredou ◽  
Nikolaos Nikoleousakos ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Signaling Pathways ◽  
Erk Signaling ◽  
In Vivo Studies ◽  
In Silico Studies ◽  
Human Ovarian Carcinoma ◽  
Dual Inhibition

(1) Background: Previous findings show that lactam steroidal alkylating esters display improved therapeutic efficacy with reduced toxicity. The aim of this study was to evaluate the anticancer activity of two newly synthesized aza-steroid alkylators (ENGA-L06E and ENGA-L08E) against human ovarian carcinoma cells, and consequently, the dual inhibition of RAS/PI3K/AKT and RAS/RAF/MEK/ERK signaling pathways, both of which are closely associated with ovarian cancer; (2) Methods: The in vitro cytostatic and cytotoxic effects of ENGA-L06E and ENGA-L08E were evaluated in a panel of five human ovarian cancer cell lines, as well as in in vivo studies. ENGA-L06E and ENGA-L08E, in addition to another two aniline-mustard alkylators, POPAM and melphalan (L-PAM), were utilized in order to determine the acute toxicity and antitumor efficacy on two human ovarian xenograft models. Also, in silico studies were performed in order to investigate the dual inhibition of ENGA-L06E and ENGA-L08E on RAS/PI3K/AKT and RAS/RAF/MEK/ERK signaling pathways; (3) Results: Both, in vitro and in vivo studies demonstrated that ENGA-L06E and ENGA-L08E were significantly more effective with a lower toxicity profile in comparison to POPAM and L-PAM alkylators. Moreover, in silico studies demonstrated that the two new aza-steroid alkylators could act as efficient inhibitors of the phosphorylation of AKT and ERK1/2 molecules; and (4) Conclusions: Both ENGA-L06E and ENGA-L08E demonstrated high anticancer activity through the inhibition of the PI3K-AKT and KRAS-ERK signaling pathways against human ovarian carcinoma, and thus constituting strong evidence towards further clinical development.

Hexachlorobenzene toxicity in the rat ovary: II. Ultrastructure induced by medium (10 mg/kg) dose exposure

1992 ◽  
Vol 50 (1) ◽  
pp. 668-669
Author(s):  
Amreek Singh ◽  
Warren G. Foster ◽  
Anna Dykeman ◽  
David C. Villeneuve
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells ◽  
Surface Epithelium ◽  
Morphological Parameters ◽  
Comprehensive Investigation ◽  
Ovary Surface Epithelium ◽  
Rat Ovary ◽  
High Doses

Hexachlorobenzene (HCB) is a known toxicant that is found in the environment as a by-product during manufacture of certain pesticides. This chlorinated chemical has been isolated from many tissues including ovary. When administered in high doses, HCB causes degeneration of primordial germ cells and ovary surface epithelium in sub-human primates. A purpose of this experiment was to determine a no-effect dose of the chemical on the rat ovary. The study is part of a comprehensive investigation on the effects of the compound on the biochemical, hematological, and morphological parameters in the monkey and rat.

Transfusion of Chick Primordial Germ Cells into Quail Embryos and their Settlement in Gonads

1998 ◽  
Vol 69 (10) ◽  
pp. 911-915 ◽  
Author(s):  
Tamao ONO ◽  
Ryohei YOKOI ◽  
Seishi MAEDA ◽  
Takao NISHIDA ◽  
Hirohiko AOYAMA
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells
Sign in / Sign up

Export Citation Format

Share Document