The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding...The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.展开更多
Background As pre-cut and pre-packaged chilled meat becomes increasingly popular,integrating the carcasscutting process into the pig industry chain has become a trend.Identifying quantitative trait loci(QTLs)of pork c...Background As pre-cut and pre-packaged chilled meat becomes increasingly popular,integrating the carcasscutting process into the pig industry chain has become a trend.Identifying quantitative trait loci(QTLs)of pork cuts would facilitate the selection of pigs with a higher overall value.However,previous studies solely focused on evaluating the phenotypic and genetic parameters of pork cuts,neglecting the investigation of QTLs influencing these traits.This study involved 17 pork cuts and 12 morphology traits from 2,012 pigs across four populations genotyped using CC1 PorcineSNP50 BeadChips.Our aim was to identify QTLs and evaluate the accuracy of genomic estimated breed values(GEBVs)for pork cuts.Results We identified 14 QTLs and 112 QTLs for 17 pork cuts by GWAS using haplotype and imputation genotypes,respectively.Specifically,we found that HMGA1,VRTN and BMP2 were associated with body length and weight.Subsequent analysis revealed that HMGA1 primarily affects the size of fore leg bones,VRTN primarily affects the number of vertebrates,and BMP2 primarily affects the length of vertebrae and the size of hind leg bones.The prediction accuracy was defined as the correlation between the adjusted phenotype and GEBVs in the validation population,divided by the square root of the trait’s heritability.The prediction accuracy of GEBVs for pork cuts varied from 0.342 to 0.693.Notably,ribs,boneless picnic shoulder,tenderloin,hind leg bones,and scapula bones exhibited prediction accuracies exceeding 0.600.Employing better models,increasing marker density through genotype imputation,and pre-selecting markers significantly improved the prediction accuracy of GEBVs.Conclusions We performed the first study to dissect the genetic mechanism of pork cuts and identified a large number of significant QTLs and potential candidate genes.These findings carry significant implications for the breeding of pork cuts through marker-assisted and genomic selection.Additionally,we have constructed the first reference populations for genomic selection of pork cuts in pigs.展开更多
Novel matrix beads for the immobilization of strain Comamonas testosteroni sp. bdq06 to degrade quino- line were fabricated from polyethersulfone（PES）. The beads have an average size of 3 mm and a surface dense laye...Novel matrix beads for the immobilization of strain Comamonas testosteroni sp. bdq06 to degrade quino- line were fabricated from polyethersulfone（PES）. The beads have an average size of 3 mm and a surface dense layer of 20 microns. To help adhesion and proliferation of bacterial cells, the surfaces of the PES beads were etched, and numerous holes about 1.5 micrometers in diameter were generated as tunnels for cell colonizing in the larger internal cavities of about 5 micrometers in diameter. The quinoline degradation was remarkably enhanced by the cells immo- bilized in PES beads compared with that by the free cells at pH 5.0 or 10.0 and a temperature of 40 ℃. The enhanced degradation of quinoline was contributed to the biofilm on the surface of PES beads, resulting in the significant re- duction of retention time from 9 h to 2 h. Furthermore, the beads remain intact after the ultrasonic treatment of them for 30 rain or recycling 50 times, indicating that they have excellent mechanical strength, flexibility and swelling ca- pacity. Thus, PES beads have great potential to be matrix for the cell immobilization in bioaugmentation.展开更多
The hippocampus is a brain region associated with memory,learning and spatial navigation,its aging-related dysfunction is a common sign of Alzheimer’s disease.Pig is a good model for human neurodegenerative disease,b...The hippocampus is a brain region associated with memory,learning and spatial navigation,its aging-related dysfunction is a common sign of Alzheimer’s disease.Pig is a good model for human neurodegenerative disease,but our understanding of the regulatory program of the pig hippocampus and its cross-species conservation in humans remains limited.Here,we profiled chromatin accessibility in 33,409 high-quality nuclei and gene expression in 8,122 high-quality nuclei of the pig hippocampus at four postnatal stages.We identified 510,908 accessible chromatin regions(ACRs)in 12 major cell types,among which progenitor cells such as neuroblasts and oligodendrocyte progenitor cells showed a dynamic decrease from early to later developmental stages.We revealed significant enrichment of transposable elements in cell type-specific ACRs,particularly in neuroblasts.We identified oligodendrocytes as the most prominent cell type with the greatest number of genes that showed significant changes during the development.We identified ACRs and key transcription factors underlying the trajectory of neurogenesis(such as POU3F3 and EGR1)and oligodendrocyte differentiation(RXRA and FOXO6).We examined 27 Alzheimer’s disease-related genes in our data and found that 15 showed cell type-specific activity(TREM2,RIN3 and CLU),and 15 genes displayed age-associated dynamic activity(BIN1,RABEP1 and APOE).We intersected our data with human genome-wide association study results to detect neurological disease-associated cell types.The present study provides a single nucleusaccessible chromatin landscape of the pig hippocampus at different developmental stages and is helpful for the exploration of pigs as a biomedical model in human neurodegenerative diseases.展开更多
Objective:Metabolic disorders are markedly common in women with polycystic ovary syndrome(PCOS),and nonalcoholic fatty liver disease(NAFLD)is observed in 30%-55%of all PCOS patients.Many studies have reported that aut...Objective:Metabolic disorders are markedly common in women with polycystic ovary syndrome(PCOS),and nonalcoholic fatty liver disease(NAFLD)is observed in 30%-55%of all PCOS patients.Many studies have reported that autophagy and apoptosis,which are closely related to mitochondrial function,play important roles in the development of NAFLD.Therefore,in this study,we aimed to explore the role of mitochondrial dysfunction caused by liver apoptosis and autophagy imbalance in the development of NAFLD in a PCOS mouse model.Methods:We used a dihydrotestosterone(DHT)-induced PCOS model to mimic the pathological process of hyperandrogenism.Hematoxylin and eosin and Oil Red O staining assays were used to observe the pathological changes in the liver.Western blotting and quantitative real-time polymerase chain reaction were used to perform mitochondrion-related assays.Results:Hepatic steatosis and different degrees of inflammation were observed in the DHT-treated mice.The expression of molecules involved in the respiratory chain and aerobic respiration process was altered.The levels of the key molecules associated with apoptosis and autophagy were abnormal.Conclusions:Androgens may play a role in the process of hepatic steatosis development by affecting mitochondrial function and subsequently inducing apoptosis and autophagy.Such phenomena might be involved in the pathogenesis of NAFLD in women with PCOS.展开更多
基金supported by the National Natural Science Foundation of China(31790410,32160781)。
文摘The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.
基金National Natural Science Foundation of China[grant number 32160782].
文摘Background As pre-cut and pre-packaged chilled meat becomes increasingly popular,integrating the carcasscutting process into the pig industry chain has become a trend.Identifying quantitative trait loci(QTLs)of pork cuts would facilitate the selection of pigs with a higher overall value.However,previous studies solely focused on evaluating the phenotypic and genetic parameters of pork cuts,neglecting the investigation of QTLs influencing these traits.This study involved 17 pork cuts and 12 morphology traits from 2,012 pigs across four populations genotyped using CC1 PorcineSNP50 BeadChips.Our aim was to identify QTLs and evaluate the accuracy of genomic estimated breed values(GEBVs)for pork cuts.Results We identified 14 QTLs and 112 QTLs for 17 pork cuts by GWAS using haplotype and imputation genotypes,respectively.Specifically,we found that HMGA1,VRTN and BMP2 were associated with body length and weight.Subsequent analysis revealed that HMGA1 primarily affects the size of fore leg bones,VRTN primarily affects the number of vertebrates,and BMP2 primarily affects the length of vertebrae and the size of hind leg bones.The prediction accuracy was defined as the correlation between the adjusted phenotype and GEBVs in the validation population,divided by the square root of the trait’s heritability.The prediction accuracy of GEBVs for pork cuts varied from 0.342 to 0.693.Notably,ribs,boneless picnic shoulder,tenderloin,hind leg bones,and scapula bones exhibited prediction accuracies exceeding 0.600.Employing better models,increasing marker density through genotype imputation,and pre-selecting markers significantly improved the prediction accuracy of GEBVs.Conclusions We performed the first study to dissect the genetic mechanism of pork cuts and identified a large number of significant QTLs and potential candidate genes.These findings carry significant implications for the breeding of pork cuts through marker-assisted and genomic selection.Additionally,we have constructed the first reference populations for genomic selection of pork cuts in pigs.
基金Supported by the National Natural Science Foundation of China（Nos.51378098, 51238001, 51408110, 51108069）, the Jilin Provincial Research Foundation, China（Nos.20130101038JC, 20140520151JH, 20080635, 2014340） and the Fundamental Research Funds for the Central Universities of China（No. 14QNJJ027）.
文摘Novel matrix beads for the immobilization of strain Comamonas testosteroni sp. bdq06 to degrade quino- line were fabricated from polyethersulfone（PES）. The beads have an average size of 3 mm and a surface dense layer of 20 microns. To help adhesion and proliferation of bacterial cells, the surfaces of the PES beads were etched, and numerous holes about 1.5 micrometers in diameter were generated as tunnels for cell colonizing in the larger internal cavities of about 5 micrometers in diameter. The quinoline degradation was remarkably enhanced by the cells immo- bilized in PES beads compared with that by the free cells at pH 5.0 or 10.0 and a temperature of 40 ℃. The enhanced degradation of quinoline was contributed to the biofilm on the surface of PES beads, resulting in the significant re- duction of retention time from 9 h to 2 h. Furthermore, the beads remain intact after the ultrasonic treatment of them for 30 rain or recycling 50 times, indicating that they have excellent mechanical strength, flexibility and swelling ca- pacity. Thus, PES beads have great potential to be matrix for the cell immobilization in bioaugmentation.
基金supported by the National Natural Science Foundation of China(32160781).
文摘The hippocampus is a brain region associated with memory,learning and spatial navigation,its aging-related dysfunction is a common sign of Alzheimer’s disease.Pig is a good model for human neurodegenerative disease,but our understanding of the regulatory program of the pig hippocampus and its cross-species conservation in humans remains limited.Here,we profiled chromatin accessibility in 33,409 high-quality nuclei and gene expression in 8,122 high-quality nuclei of the pig hippocampus at four postnatal stages.We identified 510,908 accessible chromatin regions(ACRs)in 12 major cell types,among which progenitor cells such as neuroblasts and oligodendrocyte progenitor cells showed a dynamic decrease from early to later developmental stages.We revealed significant enrichment of transposable elements in cell type-specific ACRs,particularly in neuroblasts.We identified oligodendrocytes as the most prominent cell type with the greatest number of genes that showed significant changes during the development.We identified ACRs and key transcription factors underlying the trajectory of neurogenesis(such as POU3F3 and EGR1)and oligodendrocyte differentiation(RXRA and FOXO6).We examined 27 Alzheimer’s disease-related genes in our data and found that 15 showed cell type-specific activity(TREM2,RIN3 and CLU),and 15 genes displayed age-associated dynamic activity(BIN1,RABEP1 and APOE).We intersected our data with human genome-wide association study results to detect neurological disease-associated cell types.The present study provides a single nucleusaccessible chromatin landscape of the pig hippocampus at different developmental stages and is helpful for the exploration of pigs as a biomedical model in human neurodegenerative diseases.
基金This work was supported by the National Natural Science Foundation of China(No.81673766 and 81973945 to YF,No.81572555 to XL)the Chinese Special Fund for Postdocs(No.2014T70392)+1 种基金the Swedish Medical Research Council(No.10380)the Swedish Federal Government under the LUA/ALF agreement(No.ALFGBG-147791 to HB and LS).
文摘Objective:Metabolic disorders are markedly common in women with polycystic ovary syndrome(PCOS),and nonalcoholic fatty liver disease(NAFLD)is observed in 30%-55%of all PCOS patients.Many studies have reported that autophagy and apoptosis,which are closely related to mitochondrial function,play important roles in the development of NAFLD.Therefore,in this study,we aimed to explore the role of mitochondrial dysfunction caused by liver apoptosis and autophagy imbalance in the development of NAFLD in a PCOS mouse model.Methods:We used a dihydrotestosterone(DHT)-induced PCOS model to mimic the pathological process of hyperandrogenism.Hematoxylin and eosin and Oil Red O staining assays were used to observe the pathological changes in the liver.Western blotting and quantitative real-time polymerase chain reaction were used to perform mitochondrion-related assays.Results:Hepatic steatosis and different degrees of inflammation were observed in the DHT-treated mice.The expression of molecules involved in the respiratory chain and aerobic respiration process was altered.The levels of the key molecules associated with apoptosis and autophagy were abnormal.Conclusions:Androgens may play a role in the process of hepatic steatosis development by affecting mitochondrial function and subsequently inducing apoptosis and autophagy.Such phenomena might be involved in the pathogenesis of NAFLD in women with PCOS.
