Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord ...Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans cannot.To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus database.Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes.Finally,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node connections.We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score.The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish.Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish.Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in zebrafish.Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals.展开更多
目的:拟在1008个中国人群非综合征型唇腭裂(non-syndromic oral clefts,NSOC)核心家系中探索WNT信号通路相关基因位点单体型在疾病发生风险中的作用。方法:本研究数据来自一项全基因组关联研究(genome-wide association study,GWAS),研...目的:拟在1008个中国人群非综合征型唇腭裂(non-syndromic oral clefts,NSOC)核心家系中探索WNT信号通路相关基因位点单体型在疾病发生风险中的作用。方法:本研究数据来自一项全基因组关联研究(genome-wide association study,GWAS),研究人群为“唇腭裂基因和交互作用的国际合作研究”项目在中国地区募集的806个非综合征型唇裂合并或不合并腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)核心家系和202个非综合征型单纯腭裂(non-syndromic cleft palate,NSCP)核心家系。分别在NSCL/P和NSCP家系中,通过传递不平衡检验(transmission disequilibrium test,TDT)探索基因单体型与疾病的关联。经过Bonferroni多重检验校正后,统计学检验的显著性阈值均设为P<3.47×10^(-4)。单体型关联分析通过plink(v1.07)软件完成。结果:经过数据质量控制后,NSCL/P核心家系和NSCP核心家系各纳入7个基因上的144个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点进行分析。NSCL/P家系中69个单体型与NSCL/P存在关联(P<0.05),NSCP家系中34个单体型与NSCP存在关联(P<0.05),但经过Bonferroni多重检验校正后,关联均不具有统计学意义(P>3.47×10^(-4))。结论:未发现WNT信号通路相关基因位点单体型在NSCL/P和NSCP发病风险中的作用。展开更多
基金supported by the State Key Program of National Natural Science Foundation of China,No.81330042(to SQF)the International Cooperation Program of the National Natural Science Foundation of China,No.81620108018(to SQF)
文摘Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans cannot.To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus database.Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes.Finally,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node connections.We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score.The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish.Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish.Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in zebrafish.Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals.
文摘该文探讨了RORα(retinoid acid receptor related orphan receptorα)高表达对人胃癌MGC803细胞Wnt/β-catenin信号通路靶基因的作用。采用MTT检测了MGC803细胞增殖。采用RT-PCR、Western blot与免疫共沉淀检测了Wnt/β-catenin信号通路相关分子与靶基因表达。荧光素酶报告基因方法检测c-Myc基因启动子活性。MTT结果显示,RORα高表达人胃癌MGC803细胞的增殖能力较对照组明显减弱(P<0.05)。RT-PCR与Western blot结果显示,RORα高表达组Wnt1m RNA与蛋白质水平较对照组下调(P<0.05),而β-catenin m RNA与蛋白质水平无差异(P>0.05)。免疫共沉淀结果显示,RORα高表达组RORα与β-catenin结合明显增加(P<0.05)。RORα高表达可显著下调核内β-catenin水平(P<0.05),同时可显著下调TCF-4(T cell factor-4)蛋白质水平(P<0.05)。RORα高表达可显著下调Axin、c-Myc、c-Jun m RNA与蛋白质水平(P<0.05)。荧光素酶报告基因实验结果显示,RORα高表达c-Myc启动子活性明显降低(P<0.05)。以上结果表明,RORα高表达可通过调控Wnt/β-catenin信号通路相关分子基因表达来抑制人胃癌细胞增殖。
文摘目的:拟在1008个中国人群非综合征型唇腭裂(non-syndromic oral clefts,NSOC)核心家系中探索WNT信号通路相关基因位点单体型在疾病发生风险中的作用。方法:本研究数据来自一项全基因组关联研究(genome-wide association study,GWAS),研究人群为“唇腭裂基因和交互作用的国际合作研究”项目在中国地区募集的806个非综合征型唇裂合并或不合并腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)核心家系和202个非综合征型单纯腭裂(non-syndromic cleft palate,NSCP)核心家系。分别在NSCL/P和NSCP家系中,通过传递不平衡检验(transmission disequilibrium test,TDT)探索基因单体型与疾病的关联。经过Bonferroni多重检验校正后,统计学检验的显著性阈值均设为P<3.47×10^(-4)。单体型关联分析通过plink(v1.07)软件完成。结果:经过数据质量控制后,NSCL/P核心家系和NSCP核心家系各纳入7个基因上的144个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点进行分析。NSCL/P家系中69个单体型与NSCL/P存在关联(P<0.05),NSCP家系中34个单体型与NSCP存在关联(P<0.05),但经过Bonferroni多重检验校正后,关联均不具有统计学意义(P>3.47×10^(-4))。结论:未发现WNT信号通路相关基因位点单体型在NSCL/P和NSCP发病风险中的作用。
