Grape berry shape is an important agricultural trait.Clarifying its genetic basis is significant for cultivating grape varieties that meet market demands.However,the current study by forward genetics has not achieved ...Grape berry shape is an important agricultural trait.Clarifying its genetic basis is significant for cultivating grape varieties that meet market demands.However,the current study by forward genetics has not achieved in-depth results.Here,a high-density map was constructed to identify quantitative trait loci(QTLs)for berry shape.A total of 358709 polymorphic SNPs were obtained using whole-genome resequencing(WGS)based on 208 F2 individuals derived from round grape‘E42-6’and oblong grape‘Rizamat’.The 1635.65 cM high-density map was divided into 19 linkage groups with an average distance of 0.37 cM.Using this map,three significant QTLs for fruit shape index(ShI:ratio of berry length to berry width)identified over three years were mapped onto LG4 and LG5,including one stable QTL on Chr5 with the genomic region of 0.47–1.94 Mb.Combining with gene annotation and expression patterns based on RNA-seq data from two contrasting F2 individuals with round and oblong berry(their average ShI was 1.89 and 1.10,respectively)at four developmental stages,four candidate genes were selected from the above QTLs.They were mainly involved in DNA replication,cell wall modification,and phytohormone biosynthesis.Further analysis of RNA-seq data revealed that several important phytohormone synthesis and metabolic pathways were enriched based on differentially expressed genes(DEGs),which was consistent with the results of QTL mapping for genes related to plant hormone biosynthesis in the F2 population.Furthermore,a comparison of plant hormone content showed that there were significant differences in IAA and tZ content between the two contrasting F2 individuals at different developmental stages.Our findings provide molecular insights into the genetic variation in grape berry shape.Stable QTLs and their tightly linked markers offer the possibility of marker-assisted selection to accelerate berry shape breeding.展开更多
Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading t...Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading to this difference.Methods Db/db mice and low-dose STZ injection combined with HFD-induced diabetes mellitus mice were used in this study as the model of type 2 diabetes mellitus with obesity or non-obesity.展开更多
Fibroblast activation plays a critical role in renal fibrosis,the final common pathway of chronic kidney disease(CKD).Previously,we and others reported that yes-associated protein(YAP)is activated in the renal tubular...Fibroblast activation plays a critical role in renal fibrosis,the final common pathway of chronic kidney disease(CKD).Previously,we and others reported that yes-associated protein(YAP)is activated in the renal tubular cells of fibrotic kidneys in human patients.However,the mechanisms by which YAP activation in tubular cells contributes to the activities of renal fibroblasts remain unclear.Here,we demonstrate that activation of YAP specifically in renal tubular cells induces E2F transcription factor 2(E2F2)binding and promotes fibroblast activation through the secretion of fibroblast growth factor 2(FGF2).FGF2 stimulated the activation of renal interstitial fibroblasts,which exhibited two key characteristics:enhanced synthesis of collagens and fibronectins,which are hallmarks of the fibrotic process,and increased secretion of chemoattractant cytokines that promoted the migration and activation of macrophages.The recruitment and activation of macrophages further exacerbated renal inflammation,thereby accelerating the progression of fibrogenesis.As confirmed by the clinical data,the serum levels of FGF2 were significantly higher in patients with diabetic kidney disease(DKD)and inversely correlated with the estimated glomerular filtration rate.In addition,inhibition of either YAP,E2F2,or FGF2 significantly ameliorated renal fibrosis and improved kidney function in mouse models of chronic kidney disease and renal fibrosis.Our results revealed that YAP complexed with E2F2 and promoted FGF2 expression and secretion in renal tubular cells,which in turn activated fibroblasts,followed by increased macrophage infiltration and activation.The YAP-E2F2-FGF2 axis represents a potential therapeutic target for renal fibrosis.展开更多
There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic met...There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic metabolic disorders,hepatic steatosis,intense liver inflammation and fibrosis,liver tumorigenesis,and cardiovascularcomplications.i,2"Pigment"epitheliumderived factor(PEDF)is a lipid metabolism regulator with high expression in the liver,and its reduced expression in the liver is closely related to the development of nonalcoholic fatty liver disease(NAFLD).展开更多
基金financially supported by National Key R&D Program of China(Grant No.2019YFD1001401)Project of Construction of Grape Germplasm Resources Sharing Platform(Grant No.PT2029)+2 种基金Zhengzhou Major Scientific and Technological Innovation Projects(Grant No.2020CXZX0082)National Modern Agricultural Industry Technology System Construction Special Project(Grant No.CARS-29-yc-1)Special Project of Science,Technology Innovation Project of Chinese Academy of Agricultural Sciences(Grant No.CAAS-ASTIP-2019-ZFRI).
文摘Grape berry shape is an important agricultural trait.Clarifying its genetic basis is significant for cultivating grape varieties that meet market demands.However,the current study by forward genetics has not achieved in-depth results.Here,a high-density map was constructed to identify quantitative trait loci(QTLs)for berry shape.A total of 358709 polymorphic SNPs were obtained using whole-genome resequencing(WGS)based on 208 F2 individuals derived from round grape‘E42-6’and oblong grape‘Rizamat’.The 1635.65 cM high-density map was divided into 19 linkage groups with an average distance of 0.37 cM.Using this map,three significant QTLs for fruit shape index(ShI:ratio of berry length to berry width)identified over three years were mapped onto LG4 and LG5,including one stable QTL on Chr5 with the genomic region of 0.47–1.94 Mb.Combining with gene annotation and expression patterns based on RNA-seq data from two contrasting F2 individuals with round and oblong berry(their average ShI was 1.89 and 1.10,respectively)at four developmental stages,four candidate genes were selected from the above QTLs.They were mainly involved in DNA replication,cell wall modification,and phytohormone biosynthesis.Further analysis of RNA-seq data revealed that several important phytohormone synthesis and metabolic pathways were enriched based on differentially expressed genes(DEGs),which was consistent with the results of QTL mapping for genes related to plant hormone biosynthesis in the F2 population.Furthermore,a comparison of plant hormone content showed that there were significant differences in IAA and tZ content between the two contrasting F2 individuals at different developmental stages.Our findings provide molecular insights into the genetic variation in grape berry shape.Stable QTLs and their tightly linked markers offer the possibility of marker-assisted selection to accelerate berry shape breeding.
文摘Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading to this difference.Methods Db/db mice and low-dose STZ injection combined with HFD-induced diabetes mellitus mice were used in this study as the model of type 2 diabetes mellitus with obesity or non-obesity.
基金supported by Hong Kong Research Grants Council(T12-101/23-N,SRFS20214S04,14109720,14100121,11104823)Postdoctoral Fellowship Scheme(City U PDFS2324-1S10)of the Research Grants Council of the Hong Kong SARShenzhen Overseas High-Level Talent(Peacock Plan)Project Research Initiation Programme(827000745)。
文摘Fibroblast activation plays a critical role in renal fibrosis,the final common pathway of chronic kidney disease(CKD).Previously,we and others reported that yes-associated protein(YAP)is activated in the renal tubular cells of fibrotic kidneys in human patients.However,the mechanisms by which YAP activation in tubular cells contributes to the activities of renal fibroblasts remain unclear.Here,we demonstrate that activation of YAP specifically in renal tubular cells induces E2F transcription factor 2(E2F2)binding and promotes fibroblast activation through the secretion of fibroblast growth factor 2(FGF2).FGF2 stimulated the activation of renal interstitial fibroblasts,which exhibited two key characteristics:enhanced synthesis of collagens and fibronectins,which are hallmarks of the fibrotic process,and increased secretion of chemoattractant cytokines that promoted the migration and activation of macrophages.The recruitment and activation of macrophages further exacerbated renal inflammation,thereby accelerating the progression of fibrogenesis.As confirmed by the clinical data,the serum levels of FGF2 were significantly higher in patients with diabetic kidney disease(DKD)and inversely correlated with the estimated glomerular filtration rate.In addition,inhibition of either YAP,E2F2,or FGF2 significantly ameliorated renal fibrosis and improved kidney function in mouse models of chronic kidney disease and renal fibrosis.Our results revealed that YAP complexed with E2F2 and promoted FGF2 expression and secretion in renal tubular cells,which in turn activated fibroblasts,followed by increased macrophage infiltration and activation.The YAP-E2F2-FGF2 axis represents a potential therapeutic target for renal fibrosis.
基金funded by the National Key Research and Development Program of China(No.2019YFA0801403)the National Natural Science Foundation of China(No.81670256,81970219,82170261,82000250,81741117)+2 种基金Guangdong Basic and Applied Basic Research Foundation(China)(No.2021A1515011005,2021B1212040006)China Postdoctoral Science Foundation(No.2020M672976)the Fundamental Research Funds for the Central University,Sun Yat-sen University,China(No.22qntd4808).
文摘There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic metabolic disorders,hepatic steatosis,intense liver inflammation and fibrosis,liver tumorigenesis,and cardiovascularcomplications.i,2"Pigment"epitheliumderived factor(PEDF)is a lipid metabolism regulator with high expression in the liver,and its reduced expression in the liver is closely related to the development of nonalcoholic fatty liver disease(NAFLD).
