Effects of Insulin-degrading enzyme on the proliferation of swine Sertoli cells.

Sertoli cells, the only somatic cells in testis seminiferous tubules, provide a supporting microenvironment for male germ cells and play essential roles in spermatogenesis. The insulin-degrading enzyme (IDE), a ubiquitous zinc peptidase of the inverzincin family, plays crucial role in sperm production, as IDE-knockout mice presented decreased testis weight and impaired sperm viability and morphology. However, whether and how IDE affects swine Sertoli cell proliferation remains unclear. Thus, in the present study, we aimed to evaluate the effects of IDE on the proliferation of swine Sertoli cells, as well as its underlying molecular mechanism. After knocking down IDE expression with small interfering RNA transfection, we analyzed the proliferation of swine Sertoli cells as well as the expression of related regulatory factors (WT1, ERK, and AKT). The results showed that IDE knockdown promoted swine Sertoli cell proliferation and increased WT1 expression, possibly through activating ERK and AKT. Overall, our findings suggest that IDE may be involved in male reproduction by regulating Sertoli cell proliferation, which provides new information to better understand the regulatory mechanisms of swine Sertoli cells and improve the reproductive traits of male pigs.

Characterization of A-to-I Editing in Pigs under a Long-Term High-Energy Diet.

Long-term high-energy intake has detrimental effects on pig health and elevates the risk of metabolic disease. RNA editing modifying RNA bases in a post-transcriptional process has been extensively studied for model animals. However, less evidence is available that RNA editing plays a role in the development of metabolic disorders. Here, we profiled the A-to-I editing in three tissues and six gut segments and characterized the functional aspect of editing sites in model pigs for metabolic disorders. We detected 64,367 non-redundant A-to-I editing sites across the pig genome, and 20.1% correlated with their located genes' expression. The largest number of A-to-I sites was found in the abdominal aorta with the highest editing levels. The significant difference in editing levels between high-energy induced and control pigs was detected in the abdominal aorta, testis, duodenum, ileum, colon, and cecum. We next focused on 6041 functional A-to-I sites that detected differences or specificity between treatments. We found functional A-to-I sites specifically involved in a tissue-specific manner. Two of them, located in gene SLA-DQB1 and near gene B4GALT5 were found to be shared by three tissues and six gut segments. Although we did not find them enriched in each of the gene features, in correlation analysis, we noticed that functional A-to-I sites were significantly enriched in gene 3'-UTRs. This result indicates, in general, A-to-I editing has the largest potential in the regulation of gene expression through changing the 3'-UTRs' sequence, which is functionally involved in pigs under a long-term high-energy diet. Our work provides valuable knowledge of A-to-I editing sites functionally involved in the development of the metabolic disorder.

PCSK9-D374Y Suppresses Hepatocyte Migration through Downregulating Free Cholesterol Efflux Rate and Activity of Extracellular Signal-Regulated Kinase.

Proprotein convertase subtilisin/kexin type 9 can mediate the intracellular lysosomal degradation of the low-density lipoprotein receptor protein in hepatocytes and decrease the liver's ability to scavenge low-density lipoprotein cholesterol from circulation, resulting in high levels of cholesterol in the circulatory system. Current studies have primarily focused on the relationship between PCSK9 and blood lipid metabolism; however, the biological function of PCSK9 in hepatocytes is rarely addressed. In this study, we evaluate its effects in the human hepatoma carcinoma cell line HepG2, including proliferation, migration, and free cholesterol transport. PCSK9-D374Y is a gain-of-function mutation that does not affect proliferation but significantly suppresses the migration and cholesterol efflux capacity of these cells. The suppression of the transmembrane outflow of intracellular-free cholesterol regulates small G proteins and the suppression of extracellular signal-regulated kinase. In summary, PCSK9-D374Y affects hepatocyte features, including their migration and free cholesterol transport capabilities.

Characterization of Gut Microbiota Compositions along the Intestinal Tract in CD163/pAPN Double Knockout Piglets and Their Potential Roles in Iron Absorption.

The gut microbiota is known to play a role in regulating host metabolism, yet the mechanisms underlying this regulation are not well elucidated. Our study aimed to characterize the differences in gut microbiota compositions and their roles in iron absorption between wild-type (WT) and CD163/pAPN double-gene-knockout (DKO) weaned piglets. A total of 58 samples along the entire digestive tract were analyzed for microbial community using 16S rRNA gene sequencing. The colonic microbiota and their metabolites were determined by metagenomic sequencing and untargeted liquid chromatography-mass spectrometry (LC-MS), respectively. Our results showed that no alterations in microbial community structure and composition were observed between DKO and WT weaned piglets, with the exception of colonic microbiota. Interestingly, the DKO piglets had selectively increased the relative abundance of the Leeia genus belonging to the Neisseriaceae family and decreased the Ruminococcaceae_UCG_014 genus abundance. Functional capacity analysis showed that organic acid metabolism was enriched in the colon in DKO piglets. In addition, the DKO piglets showed increased iron levels in important tissues compared with WT piglets without any pathological changes. Pearson's correlation coefficient indicated that the specific bacteria such as Leeia and Ruminococcaceae_UCG_014 genus played a key role in host iron absorption. Moreover, the iron levels had significantly (P < 0.05) positive correlation with microbial metabolites, particularly carboxylic acids and their derivatives, which might increase iron absorption by preventing iron precipitation. Overall, this study reveals an interaction between colonic microbiota and host metabolism and has potential significance for alleviating piglet iron deficiency. IMPORTANCE Iron deficiency is a major risk factor for iron deficiency anemia, which is among the most common nutritional disorders in piglets. However, it remains unclear how the gut microbiota interacts with host iron absorption. The current report provides the first insight into iron absorption-microbiome connection in CD163/pAPN double knockout piglets. The present results showed that carboxylic acids and their derivatives contributed to the absorption of nonheme iron by preventing ferric iron precipitation.

Molecular Characteristics and Promoter Analysis of Porcine COL1A1.

COL1A1 encodes the type I collagen α1 chain, which shows the highest abundance among members of the collagen family and is widely expressed in different mammalian cells and tissues. However, its molecular characteristics are not completely elucidated. In this study, the molecular profiles of COL1A1 and characteristics of the COL1A1 protein were investigated using a promoter activity assay and multiple bioinformatics tools. The results showed that the 5' flanking region of porcine COL1A1 contained two CpG islands, five core promoter sequences, and twenty-six transcription factor-binding sites. In the luciferase assay, the upstream 294 bp region of the initiation codon of COL1A1 showed the highest activity, confirming that this section is the core region of the porcine COL1A1 promoter. Bioinformatic analysis revealed that COL1A1 is a negatively charged, hydrophilic secreted protein. It does not contain a transmembrane domain and is highly conserved in humans, mice, sheep, and pigs. Protein interaction analysis demonstrated that the interaction coefficient of COL1A1 with COL1A2, COL3A1, ITGB1, and ITGA2 was greater than 0.9, suggesting that this protein plays a crucial role in collagen structure formation and cell adhesion. These results provide a theoretical basis for further investigation of the functions of porcine COL1A1.

Spatial and Temporal Expression Characteristics of the HBB Gene Family in Six Different Pig Breeds.

ß-Thalassemia induces hemolytic anemia caused by mutations in the ß-chain gene locus. As humans progress from embryo to adulthood, hemoglobin recombines twice. To test whether similar hemoglobin reassembly occurs in pigs, bioinformatics tools were used to predict the pig hemoglobin-encoding gene. We then systematically analyzed the expression patterns of the HBB gene family in three developmental stages (weaning, sexual maturity and physical maturity) of six different pig breeds (Landrace, Yorkshire, Wuzhishan, Songliao black, Meishan and Tibetan). The results showed that the new hemoglobin coding gene 'HBB-like' was found in pigs, while the HBG gene did not exist in pigs, indicating that human-like reassembly might not exist in pigs. The HBB and HBB-like genes shared highly similar amino acid sequences and gene sequences. The genes on the ß-chain were highly similar between humans and pigs and the amino acid sequences of human and pig HBB genes at position 26 and positions 41-42 were identical. qPCR results showed that there were significant differences in the spatiotemporal expression patterns of the four genes (HBA, HBB, HBB-like and HBE) across breeds. Our results provide a foundation for follow-up studies assessing the relationship between the gene-encoding hemoglobin and ß-thalassemia disease, as well as the construction of a gene-edited ß-thalassemia miniature pig model to assess ß-thalassemia treatments.

Prmt7 Downregulation in Mouse Spermatogonia Functions through miR-877-3p/Col6a3.

Protein arginine methyltransferases 7 (Prmt7) is expressed in male germ cells, including primordial germ cells, gonocytes, and spermatogonia. Our previous study demonstrated that Prmt7 downregulation reduced the proliferation of GC-1 cells (a cell line of mouse immortalized spermatogonia). However, how Prmt7 regulates spermatogonial proliferation through miRNA and the target gene remains elusive. Here, we experimentally reduced the Prmt7 expression in the GC-1 cells and subjected them to miRNA sequencing to explore the miRNA profile and its Prmt7-responsive members. In total, 48 differentially expressed miRNAs (DEmiRNAs), including 36 upregulated and 12 downregulated miRNAs, were identified. After verifying the validity of sequencing results through qRT-PCR assays in randomly selected DEmiRNAs, we predicted the target genes of these DEmiRNAs. Next, we combined DEmiRNA target genes and previously identified differentially expressed genes between Prmt7 knockdown and control groups of GC-1 cells, which resulted in seven miRNA/target gene pairs. Among these miRNA/target gene pairs, we further detected the expression of Col6a3 (collagen type VI alpha 3) as the target gene of mmu-miR-877-3p. The results suggested that Prmt7 downregulation in mouse spermatogonia might function through miR-877-3p/Col6a3. Overall, these findings provide new insights into the role of Prmt7 in male germ cell development through miRNA and target genes.

Pnpla5-knockout rats exhibit reduced expression levels of proteins involved in steroid metabolism and wound healing compared to wild-type rats.

BACKGROUND: Patatin-like phospholipase domain containing 5 (PNPLA5) is a newly-discovered lipase. Although the PNPLA family plays critical roles in diverse biological processes, the biological functions of PNPLA5 mostly unknown. We previously found that the deletion of Pnpla5 in rats causes a variety of phenotypic abnormalities. In this study, we further explored the effects of Pnpla5 knockout (KO) on male rats. RESULTS: The body weight and testicular or epididymal tissue weight of three to six 3-month-old Pnpla5 KO or wild-type (WT) male Sprague-Dawley rats were measured. The protein expression levels were also measured via western blotting and iTRAQ (isobaric tags for relative and absolute quantitation) analyses. No significant difference between Pnpla5 KO and WT rats, regarding body weight, testicular or epididymal tissue weight, or hormone levels, were found. However, the relative testicular tissue weight of the KO (Pnpla5-/-) rats was higher (P < 0.05) than that of WT rats. Significant increases in apoptotic cells numbers (P < 0.001) and BAX and Caspase-9 expression levels were observed in the testicular tissue of Pnpla5-/- rats. Moreover, iTRAQ analysis revealed that the levels of proteins involved in steroid metabolism and wound healing were significantly decreased in Pnpla5-/- rats. CONCLUSION: This study revealed that Pnpla5 knockout induced apoptosis in rat testes. We also ascertained that Pnpla5 plays an important role in lipid metabolism, wound healing, and affects reproductive organs negatively, providing new target genes and pathways that can be analyzed to unravel the biological function of Pnpla5.

Enhancing Animal Disease Resistance, Production Efficiency, and Welfare through Precise Genome Editing.

The major goal of animal breeding is the genetic enhancement of economic traits. The CRISPR/Cas system, which includes nuclease-mediated and base editor mediated genome editing tools, provides an unprecedented approach to modify the mammalian genome. Thus, farm animal genetic engineering and genetic manipulation have been fundamentally revolutionized. Agricultural animals with traits of interest can be obtained in just one generation (and without long time selection). Here, we reviewed the advancements of the CRISPR (Clustered regularly interspaced short palindromic repeats)/Cas (CRISPR associated proteins) genome editing tools and their applications in animal breeding, especially in improving disease resistance, production performance, and animal welfare. Additionally, we covered the regulations on genome-edited animals (GEAs) and ways to accelerate their use. Recommendations for how to produce GEAs were also discussed. Despite the current challenges, we believe that genome editing breeding and GEAs will be available in the near future.

Changes in the Mucosa-Associated Microbiome and Transcriptome across Gut Segments Are Associated with Obesity in a Metabolic Syndrome Porcine Model.

Several studies have suggested a role for gut mucosa-associated microbiota in the development of obesity, but the mechanisms involved are poorly defined. Here, the impact of the gut mucosa-associated microbiota on obesity and related metabolic disorders was evaluated in a metabolic syndrome (MetS) porcine model. Body composition was determined among male Wuzhishan minipigs consuming a high-energy diet (HED) and compared to that of those consuming a normal diet (ND), and gut segments (duodenum, jejunum, ileum, cecum, colon, and rectum) were sampled for paired analysis of mucosa-associated microbiota and transcriptome signatures with 16S rRNA gene and RNA sequencing, respectively. Our data indicated that long-term HED feeding significantly increased body weight and visceral fat deposition and aggravated metabolic disorders. Specially, HED feeding induced mucosa-associated microbiota dysbiosis and selectively increased the abundance of the families Enterobacteriaceae, Moraxellaceae, and Lachnospiraceae in the upper intestine. The association analysis indicated that specific bacteria play key roles in adiposity, e.g., Lactobacillus johnsonii in the duodenum, Actinobacillus indolicus in the jejunum, Acinetobacter johnsonii in the ileum, Clostridium butyricum in the cecum, Haemophilus parasuis in the colon, and bacterium NLAEzlP808, Halomonas taeheungii, and Shewanella sp. JNUH029 in the rectum. Transcriptome data further revealed intestinal lipid metabolism and immune dysfunction in the MetS individuals, which may be associated with obesity and related metabolic disorders. Our results indicated that gut mucosa-associated microbiota dysbiosis has the potential to exacerbate obesity, partially through modulating systemic inflammatory responses. IMPORTANCE Obesity is a major risk factor for metabolic syndrome, which is the most common cause of death worldwide, especially in developed countries. The link between obesity and gut mucosa-associated microbiota is unclear due to challenges associated with the collection of intestinal samples from humans. The current report provides the first insight into obesity-microbiome-gut immunity connections in a metabolic syndrome (MetS) porcine model. The present results show that dysbiosis of mucosal microbiota along the entire digestive tract play a critical role in the proinflammatory response in the host-microbial metabolism axis, resulting in obesity and related metabolic disorders in the MetS model.

Myostatin Alteration in Pigs Enhances the Deposition of Long-Chain Unsaturated Fatty Acids in Subcutaneous Fat.

In animals, myostatin (MSTN) is a negative regulator that inhibits muscle growth and repair. The decreased level of functional MSTN gene expression can change the amount and proportions of fats in pigs. In this study we determined the lipidomics of subcutaneous fat in MSTN single copy mutant pigs and evaluated the variations in lipid contents of the subcutaneous fat from MSTN+/- and wild type Large White (LW) pigs via ultra-performance liquid chromatography-quadrupole/Orbitrap-mass spectrometry (MS). The results showed that the quantities of glycerolipids, sphingolipids, fatty acyls and glycerophospholipids were significantly changed, particularly, the molecular diacylglycerol in glycerolipids, long-chain unsaturated fatty acids, and ceramide non-hydroxy fatty acid-sphingosine in sphingolipids were remarkably increased in the MSTN+/- group. Due to their positive bioavailability demonstrated by previous researches, these three lipids might be beneficial for human health. Further, the results of our study confirm that MSTN participates in the regulation of fat metabolism, and reduced expression of MSTN can ultimately influence the accumulation of lipid contents in the subcutaneous fat of pigs.

Multi-Omic Analysis in a Metabolic Syndrome Porcine Model Implicates Arachidonic Acid Metabolism Disorder as a Risk Factor for Atherosclerosis.

Background: The diet-induced gut microbiota dysbiosis has been suggested as a major risk factor for atherothrombosis, however, the detailed mechanism linking these conditions is yet to be fully understood. Methods: We established a long-term excessive-energy diet-induced metabolic syndrome (MetS) inbred Wuzhishan minipig model, which is characterized by its genetic stability, small size, and human-like physiology. The metabolic parameters, atherosclerotic lesions, gut microbiome, and host transcriptome were analyzed. Metabolomics profiling revealed a linkage between gut microbiota and atherothrombosis. Results: We showed that white atheromatous plaque was clearly visible on abdominal aorta in the MetS model. Furthermore, using metagenome and metatranscriptome sequencing, we discovered that the long-term excessive energy intake altered the local intestinal microbiota composition and transcriptional profile, which was most dramatically illustrated by the reduced abundance of SCFAs-producing bacteria including Bacteroides, Lachnospiraceae, and Ruminococcaceae in the MetS model. Liver and abdominal aorta transcriptomes in the MetS model indicate that the diet-induced gut microbiota dysbiosis activated host chronic inflammatory responses and significantly upregulated the expression of genes related to arachidonic acid-dependent signaling pathways. Notably, metabolomics profiling further revealed an intimate linkage between arachidonic acid metabolism and atherothrombosis in the host-gut microbial metabolism axis. Conclusions: These findings provide new insights into the relationship between atherothrombosis and regulation of gut microbiota via host metabolomes and will be of potential value for the treatment of cardiovascular diseases in MetS.

Viscera Characteristics of MSTN-Edited Heterozygous Pigs.

Myostatin (MSTN) is a protein that negatively regulates growth of skeletal muscle, and inactivation of MSTN improves the mass of skeletal muscle. Our previous work found that MSTN +/- pigs have higher muscle depth and lower fat depth compared to wild type without any developmental problems. Therefore, MSTN-edited pigs are most likely to appear as heterozygotes in the potential future market, but the characteristics of organs in digestive and reproductive system of pigs with MSTN gene editing remains unclear. Here, we investigated the histological of the organs in the digestive system and reproductive system in MSTN gene heterozygotes at adult stages. The length of intestine was further compared between adult heterozygous and wild type pigs. We found no significant differences in histomorphology of organs, including heart, duodenum, jejunum, ileum, cecum, colon, testis, epididymis, ovaries, oviducts and uterus, between individuals from two genotypes. Moreover, there was no significant difference in the average length of intestine in adult pigs. Our data provide a reference for further clarifying the applications of MSTN gene edited pigs.

A transgene-free method for rapid and efficient generation of precisely edited pigs without monoclonal selection.

Gene-edited pigs for agricultural and biomedical applications are typically generated using somatic cell nuclear transfer (SCNT). However, SCNT requires the use of monoclonal cells as donors, and the time-consuming and laborious monoclonal selection process limits the production of large populations of gene-edited animals. Here, we developed a rapid and efficient method named RE-DSRNP (reporter RNA enriched dual-sgRNA/CRISPR-Cas9 ribonucleoproteins) for generating gene-edited donor cells. RE-DSRNP takes advantage of the precise and efficient editing features of dual-sgRNA and the high editing efficiency, low off-target effects, transgene-free nature, and low cytotoxic characteristics of reporter RNA enriched RNPs (CRISPR-Cas9 ribonucleoproteins), thus eliminating the need for the selection of monoclonal cells and thereby greatly reducing the generation time of donor cells from 3-4 weeks to 1 week, while also reducing the extent of apoptosis and chromosomal aneuploidy of donor cells. We applied RE-DSRNP to produce cloned pigs bearing a deletion edit of the wild-type p53-induced phosphatase 1 (WIP1) gene: among 32 weaned cloned pigs, 31 (97%) carried WIP1 edits, and 15 (47%) were homozygous for the designed fragment deletion, and no off-target event was detected. The WIP1 knockout (KO) pigs exhibited male reproductive disorders, illustrating the utility of RE-DSRNP for rapidly generating precisely edited animals for functional genomics and disease research. RE-DSRNP's strong editing performance in a large animal and its marked reduction in the required time for producing SCNT donor cells support its application prospects for rapidly generating populations of transgene-free cloned animals.

Long-term, multidomain analyses to identify the breed and allelic effects in MSTN-edited pigs to overcome lameness and sustainably improve nutritional meat production.

Beef and mutton production has been aided by breeding to integrate allelic diversity for myostatin (MSTN), but a lack of diversity in the MSTN germplasm has limited similar advances in pig farming. Moreover, insurmountable challenges with congenital lameness and a dearth of data about the impacts of feed conversion, reproduction, and meat quality in MSTN-edited pigs have also currently blocked progress. Here, in a largest-to-date evaluation of multiple MSTN-edited pig populations, we demonstrated a practical alternative edit-site-based solution that overcomes the major production obstacle of hindlimb weakness. We also provide long-term and multidomain datasets for multiple breeds that illustrate how MSTN-editing can sustainably increase the yields of breed-specific lean meat and the levels of desirable lipids without deleteriously affecting feed-conversion rates or litter size. Apart from establishing a new benchmark for the data scale and quality of genome-edited animal production, our study specifically illustrates how gene-editing site selection profoundly impacts the phenotypic outcomes in diverse genetic backgrounds.

Safety evaluation of transgenic and genome-edited food animals.

There is an urgent need to reform the regulation of transgenic and genome-edited food animals. Now is the time to simplify regulatory safety guidelines based on science before it is too late to have these animals in place to meet societal needs in coming decades.

Integrated analysis of DNA methylome and transcriptome reveals the differences in biological characteristics of porcine mesenchymal stem cells.

BACKGROUND: Bone marrow (BM) and umbilical cord (UC) are the main sources of mesenchymal stem cells (MSCs). These two MSCs display significant differences in many biological characteristics, yet the underlying regulation mechanisms of these cells remain largely unknown. RESULTS: BMMSCs and UCMSCs were isolated from inbred Wuzhishan miniature pigs and the first global DNA methylation and gene expression profiles of porcine MSCs were generated. The osteogenic and adipogenic differentiation ability of porcine BMMSCs is greater than that of UCMSCs. A total of 1979 genes were differentially expressed and 587 genes were differentially methylated at promoter regions in these cells. Integrative analysis revealed that 102 genes displayed differences in both gene expression and promoter methylation. Gene ontology enrichment analysis showed that these genes were associated with cell differentiation, migration, and immunogenicity. Remarkably, skeletal system development-related genes were significantly hypomethylated and upregulated, whereas cell cycle genes were opposite in UCMSCs, implying that these cells have higher cell proliferative activity and lower differentiation potential than BMMSCs. CONCLUSIONS: Our results indicate that DNA methylation plays an important role in regulating the differences in biological characteristics of BMMSCs and UCMSCs. Results of this study provide a molecular theoretical basis for the application of porcine MSCs in human medicine.

The Effects of Flavonoid Apigenin on Male Reproductive Health: Inhibition of Spermatogonial Proliferation through Downregulation of Prmt7/Akt3 Pathway.

Apigenin, a common dietary flavonoid abundantly present in a variety of fruits and vegetables, has promising anticancer properties. As an effector of apigenin in myoblasts, protein arginine methyltransferase 7 (Prmt7) is required for male germ cell development. However, whether apigenin may influence male reproductive health through Prmt7 is still unclear. To this end, mouse spermatogonia were treated with different concentrations (2.5 to 50 µM) of apigenin for 48 h, which showed that apigenin could cause reduced cell proliferation in conjunction with longer S phase and G2/M phase (with concentrations of 10 and 20 µM, respectively), and increased apoptosis of spermatogonia (with concentration of 20 µM). Reduced Prmt7 expression was found in 20 µM apigenin-treated spermatogonia. Moreover, siRNA-induced Prmt7 knockdown exhibited similar influence on spermatogonia as that of apigenin treatment. In mechanistic terms, transcriptome analysis revealed 287 differentially expressed genes between Prmt7-downregulated and control spermatogonia. Furthermore, rescue experiments suggested that the effects of apigenin on spermatogonia might be mediated through the Prmt7/Akt3 pathway. Overall, our study supports that apigenin can interfere with mouse spermatogonial proliferation by way of the downregulated Prmt7/Akt3 pathway, which demonstrates that the concentration should be taken into account in future applications of apigenin for cancer therapy of men.

PRMT7: A Pivotal Arginine Methyltransferase in Stem Cells and Development.

Protein arginine methylation is a posttranslational modification catalyzed by protein arginine methyltransferases (PRMTs), which play critical roles in many biological processes. To date, nine PRMT family members, namely, PRMT1, 2, 3, 4, 5, 6, 7, 8, and 9, have been identified in mammals. Among them, PRMT7 is a type III PRMT that can only catalyze the formation of monomethylarginine and plays pivotal roles in several kinds of stem cells. It has been reported that PRMT7 is closely associated with embryonic stem cells, induced pluripotent stem cells, muscle stem cells, and human cancer stem cells. PRMT7 deficiency or mutation led to severe developmental delay in mice and humans, which is possibly due to its crucial functions in stem cells. Here, we surveyed and summarized the studies on PRMT7 in stem cells and development in mice and humans and herein provide a discussion of the underlying molecular mechanisms. Furthermore, we also discuss the roles of PRMT7 in cancer, adipogenesis, male reproduction, cellular stress, and cellular senescence, as well as the future perspectives of PRMT7-related studies. Overall, PRMT7 mediates the proliferation and differentiation of stem cells. Deficiency or mutation of PRMT7 causes developmental delay, including defects in skeletal muscle, bone, adipose tissues, neuron, and male reproduction. A better understanding of the roles of PRMT7 in stem cells and development as well as the underlying mechanisms will provide information for the development of strategies for in-depth research of PRMT7 and stem cells as well as their applications in life sciences and medicine.

Social acceptance for commercialization of genetically modified food animals.

Genetically modified food animals (GMFAs) are needed to address early the cumulative effects of livestock production on the environment, and to accommodate future food demands. In 2020 China and the USA, the world's two largest economies, embarked on regulatory reforms to boost the commercialization of such animals. However, gaining social acceptance of GMFAs for commercialization remains a global challenge. We propose a framework that focuses on social license for commercialization of GMFAs by defining four classes of improvement using precision genetics: (1) animals equivalent to natural variation to obtain the improved effect of cross-breeding (ENV); (2) animals with an inactivated gene that could occur via natural mutation (ENC-); (3) animals harboring a natural genetic sequence isolated from another species (ENC+); and (4) animals with synthetic sequences encoding novel genes (BNE). Our approach can guide regulators and the public to support orderly commercialization of GMFAs.