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Generation of live mice from haploid ESCs with germline-DMR deletions or switch

Genomic imprinting is required for sexual reproduction and embryonic development of mammals, in which, differentially methylated regions (DMRs) regulate the parent-specific monoallelic expression of imprinted genes. Numerous studies on imprinted genes have highlighted their critical roles in development. However, what imprinting network is essential for development is still unclear. Here, we establish a stepwise system to reconstruct a development-related imprinting network, in which diploid embryonic stem cells (ESCs) are derived by fusing between parthenogenetic (PG)- and androgenetic (AG)-haploid embryonic stem cells (haESCs) with different DMR deletions (termed Ha-Ha-fusion system), followed by tetraploid complementation to produce all-haESC fetuses. Diploid ESCs fused between PG-haESCs carrying 8 maternally-derived DMR deletions and AG-haESCs with 2 paternally-derived DMR deletions give rise to live pups efficiently, among which, one lives to weaning. Strikingly, diploid ESCs derived from the fusion of PG-haESCs with 7 maternal DMR deletions and AG-haESCs with 2 paternal DMR deletions and maternal Snrpn-DMR deletion also support full-term embryonic development. Moreover, embryos reconstructed by injection of AG-haESCs with hypomethylated H19-DMR into oocytes with H19-DMR deletion develop into live mice sustaining inverted allelic gene expression. Together, our findings indicate that restoration of monoallelic expression of 10 imprinted regions is adequate for the full-term development of all-haESC pups, and it works irrespective of their parental origins. Meanwhile, Ha-Ha-fusion system provides a useful tool for deciphering imprinting regulation networks during embryonic development.

Maternal effects in the model system Daphnia: the ecological past meets the epigenetic future

Maternal effects have been shown to play influential roles in many evolutionary and ecological processes. However, understanding how environmental stimuli induce within-generation responses that transverse across generations remains elusive, particularly when attempting to segregate confounding effects from offspring genotypes. This review synthesizes literature regarding resource- and predation-driven maternal effects in the model system Daphnia, detailing how the maternal generation responds to the environmental stimuli and the maternal effects seen in the offspring generation(s). Our goal is to demonstrate the value of Daphnia as a model system by showing how general principles of maternal effects emerge from studies on this system. By integrating the results across different types of biotic drivers of maternal effects, we identified broadly applicable shared characteristics: 1. Many, but not all, maternal effects involve offspring size, influencing resistance to starvation, infection, predation, and toxins. 2. Maternal effects manifest more strongly when the offspring’s environment is poor. 3. Strong within-generation responses are typically associated with strong across-generation responses. 4. The timing of the maternal stress matters and can raise or lower the magnitude of the effect on the offspring’s phenotype. 5. Embryonic exposure effects could be mistaken for maternal effects. We outline questions to prioritize for future research and discuss the possibilities for integration of ecologically relevant studies of maternal effects in natural populations with the molecular mechanisms that make them possible, specifically by addressing genetic variation and incorporating information on epigenetics. These small crustaceans can unravel how and why non-genetic information gets passed to future generations.

Melatonin affects trophoblast epithelial-to-mesenchymal transition and oxidative damage resistance by modulating GDF15 expression to promote embryo implantation

Melatonin is widely observed in the female reproductive system and regulates trophoblast cell functions, but its effects on embryo implantation and underlying mechanisms are not well understood. By constructing an in vitro embryo culture model, we found that melatonin enhances migration and implantation in human and mouse trophoblast cells. It also significantly promoted HTR-8/SVneo cell proliferation, inhibited apoptosis, enhanced migration, and mitigated oxidative damage. Further investigation revealed that melatonin promoted trophoblast cell migration and increased the in vitro implantation rate of HTR-8/SVneo spheroids by promotes epithelial-mesenchymal transition (EMT) via the growth differentiation factor 15 (GDF15)–mothers against decapentaplegic homolog 2/3 (SMAD2/3) pathway. Additionally, melatonin increased the levels of glutathione peroxidase 4 (GPX4) and glutathione (GSH) in HTR-8/SVneo cells by upregulating the expression of GDF15, inhibiting reactive oxygen species (ROS) accumulation, and increasing mitochondrial membrane potential, thus suppressing apoptosis during oxidative stress. In conclusion, melatonin promotes EMT in trophoblast cells via GDF15-SMAD2/3 pathway and partially induces the expression of GPX4 through GDF15 to enhance oxidative damage resistance in trophoblast cells. These findings highlight melatonin’s regulatory role in embryo implantation and suggest new avenues for exploring its biological effects in reproduction and clinical applications.

Investigating the role of psychological elements in advancing IT skills among accounting students: insights from Saudi Arabia

Psychological factors are among the multiple influences on people’s daily behavior. The outcomes of various daily activities, ranging from success to failure, are often determined by these psychological aspects. The purpose of this research is to determine how psychological factors influence the skill of accounting students in Saudi Arabia with regard to information technology (IT). In order to achieve the research objectives, a descriptive and explanatory research design incorporating a quantitative approach is utilized. The study’s target population comprises accounting students from government universities in Saudi Arabia. Data collection employed a combination of convenient and snowball sampling strategies, ensuring broader applicability of the findings. A total of 306 accounting students from these universities participated in an online survey. Data analysis is conducted using partial least squares-structural equation modeling (PLS-SEM), and the significance of path coefficients is assessed through bootstrapping tests. Results indicated that motor skills, visual processing, fatigue, and stress positively influence IT skill development in these students. Conversely, ergonomics and cognitive abilities appeared to have no significant effect. The model accounted for approximately 65% of the variance in IT skill development among university students. These insights can guide educational institutions in formulating strategic plans for IT skill development, ensuring students acquire the necessary competencies on campus. Additionally, the findings offer valuable information for government bodies developing standards to foster IT skill growth.

Direct specification of lymphatic endothelium from mesenchymal progenitors

During embryogenesis, endothelial cells (ECs) are generally described to arise from a common pool of progenitors termed angioblasts, which diversify through iterative steps of differentiation to form functionally distinct subtypes of ECs. A key example is the formation of lymphatic ECs (LECs), which are thought to arise largely through transdifferentiation from venous endothelium. Opposing this model, here we show that the initial expansion of mammalian LECs is primarily driven by the in situ differentiation of mesenchymal progenitors and does not require transition through an intermediate venous state. Single-cell genomics and lineage-tracing experiments revealed a population of paraxial mesoderm-derived Etv2+Prox1+ progenitors that directly give rise to LECs. Morphometric analyses of early LEC proliferation and migration, and mutants that disrupt lymphatic development supported these findings. Collectively, this work establishes a cellular blueprint for LEC specification and indicates that discrete pools of mesenchymal progenitors can give rise to specialized subtypes of ECs.

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