The development of primordial germ cells (PGCs) undergoes epigenetic modifications. The study of histone methylation in regulating PGCs is beneficial to understand the development and differentiation mechanism of germ stem cells. Notably, it provides a theoretical basis for directed induction and mass acquisition in vitro. However, little is known about the regulation of PGC formation by histone methylation. Here, we found the high enrichment of H3K4me2 in the blastoderm, genital ridges, and testis. Chromatin immunoprecipitation sequencing was performed and the results revealed that genomic H3K4me2 is dynamic in embryonic stem cells, PGCs, and spermatogonial stem cells. This trend was consistent with the H3K4me2 enrichment in the gene promoter region. Additionally, narrow region triggered PGC‐related genes (Bmp4, Wnt5a, and Tcf7l2) and signaling pathways (Wnt and transforming growth factor‐β). After knocking down histone methylase Mll2 in vitro and vivo, the level of H3K4me2 decreased, inhibiting Cvh and Blimp1 expression, then repressing the formation of PGCs. Taken together, our study revealed the whole genome map of H3K4me2 in the formation of PGCs, contributing to improve the epigenetic study in PGC formation and providing materials for bird gene editing and rescue of endangered birds. 相似文献
The imbalance between excess reactive oxygen species (ROS) generation and insufficient antioxidant defenses contribute to a range of neurodegenerative diseases. High ROS levels damage cellular macromolecules such as DNA, proteins and lipids, leading to neuron vulnerability and eventual death. However, the underlying molecular mechanism of the ROS regulation is not fully elucidated. Recently, an increasing number of studies suggest that microRNAs (miRNAs) emerge as the targets in regulating oxidative stress. We recently reported the neuroprotective effect of miR-137-3p for brachial plexus avulsion-induced motoneuron death. The present study is sought to investigate whether miR-137-3p also could protect PC12 cells against hydrogen peroxide (H2O2) induced neurotoxicity. By using cell viability assay, ROS assay, gene and protein expression assay, we found that PC-12 cells exposed to H2O2 exhibited decreased cell viability, increased expression levels of calpain-2 and neuronal nitric oxide synthase (nNOS), whereas a decreased miR-137-3p expression. Importantly, restoring the miR-137-3p levels in H2O2 exposure robustly inhibited the elevated nNOS, calpain-2 and ROS expression levels, which subsequently improved the cell viability. Furthermore, the suppressive effect of miR-137-3p on the elevated ROS level under oxidative stress was considerably blunted when we mutated the binding site of calpain-2 targted by miR-137-3p, suggesting the critical role of calpain-2 involving the neuroprotective effect of miR-137-3p. Collectively, these findings highlight the neuroprotective role of miR-137-3p through down-regulating calpain and NOS activity, suggesting its potential role for combating oxidative stress insults in the neurodegenerative diseases.
Virologica Sinica - Influenza A viruses (IAV) are responsible for seasonal flu epidemics, which can lead to high morbidity and mortality each year. Like other viruses, influenza virus can hijack... 相似文献
Natural selection serves as an important agent to drive and maintain interspecific divergence. Populus rotundifolia Griff. is an alpine aspen species that mainly occurs in the Qinghai–Tibet Plateau (QTP) and adjacent highlands, whereas its sister species, P. davidiana Dode, is distributed across southwest and central to northeast China in much lower altitude regions. In this study, we collected genome resequencing data of 53 P. rotundifolia and 42 P. davidiana individuals across their natural distribution regions. Our population genomic data suggest that the two species are well delimitated in the allopatric regions, but with hybrid zones in their adjacent region in the eastern QTP. Coalescent simulations suggest that P. rotundifolia diverged from P. davidiana in the middle Pleistocene with following continuous gene flow since divergence. In addition, we found numerous highly diverged genes with outlier signatures that are likely associated with high-altitude adaptation of these alpine aspens. Our finding indicate that Quaternary climatic changes and natural selection have greatly contributed to the origin and distinction maintenance of P. rotundifolia in the QTP. 相似文献
The diversity of axon guidance (AG) receptors reflects gains in complexity of the animal nervous system during evolution. Members of the Roundabout (Robo) family of receptors interact with Slit proteins and play important roles in many developmental processes, including AG and neural crest cell migration. There are four members of the Robo gene family. However, the evolutionary history of Robo family genes remain obscure. We analyzed the distribution of Robo family members in metazoan species ranging in complexity from hydras to humans. We undertook a phylogenetic analysis in metazoans, synteny analysis, and ancestral chromosome mapping in vertebrates, and detected selection pressure and functional divergence among four mammalian Robo paralogs. Based on our analysis, we proposed that the ancestral Robo gene could have undergone a tandem duplication in the vertebrate ancestor; then one round of whole genome duplication events occurred before the divergence of ancestral lamprey and gnathostome, generating four paralogs in early vertebrates. Robo4 paralog underwent segmental loss in the following evolutionary process. Our results showed that Robo3 paralog is under more powerful purifying selection pressure compared with other three paralogs, which could correlate with its unique expression pattern and function. Furthermore, we found four sites under positive selection pressure on the Ig1‐2 domains of Robo4 that might interfere with its binding to Slits ligand. Diverge analysis at the amino acid level showed that Robo4 paralog have relatively greater functional diversifications than other Robo paralogs. This coincides with the fact that Robo4 predominantly functions in vascular endothelial cells but not the nervous system. 相似文献
Science China Life Sciences - Prolonged viral RNA shedding and recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID-19) patients have been... 相似文献
Dear Editor,
Primary localized cutaneous amyloidosis (PLCA) is a skin-limited disorder characterized by deposition of amyloid material in the superficial dermis.According to clinical characteristics,PLCA is divided into lichen,macular,and nodular amyloidosis.PLCA is found worldwide but has a higher incidence in South America and Southeast Asia,such as in Brazil and China (Chang et al.,2014;Tey et al.,2016). 相似文献
Paper is increasingly recognized as a portable substrate for cell culture, due to its low-cost, flexible, and special porous property, which provides a native cellular 3D microenvironment. Therefore, paper-based microfluidics has been developed for cell culture and biomedical analysis. However, the inability of continuous medium supply limits the wide application of paper devices for cell culture. Herein, a paper-based microfluidic device is developed with novel folded paper strips as wick-like structure, which is used for medium self-driven perfusion. The paper with patterns of hydrophilic channel, culture areas, and hydrophobic barrier could be easily fabricated through wax-printing. After printing, the hydrophilic paper strip at the periphery of the lower layer is then folded at 90° and extended into the medium container for continuous automatic supply of medium to the cell culture area. Tumor cells cultured in the paper device are tested for anti-cancer drug screening. Visualized cell viability and chemical sensitivity testing can be achieved by colorimetry combined with simple smartphone imaging, effectively reducing precision instrument dependence. The wick paper-based microfluidic device for cell culture endows the method the advantages of lower cost, ease-of-operation, miniaturization, and shows a great potential for large-scale cell culture, antibody drug production, and efficient screening. 相似文献