孤独症(即自闭症谱系障碍)是最常见的儿童中枢神经系统发育紊乱疾病。目前尚无特效治疗药物。最新的突破性进展是通过外显子组测序发现了一批与孤独症相关的单基因新发突变(de novo mutation)。在筛查到的众多孤独症相关新突变基因中,...孤独症(即自闭症谱系障碍)是最常见的儿童中枢神经系统发育紊乱疾病。目前尚无特效治疗药物。最新的突破性进展是通过外显子组测序发现了一批与孤独症相关的单基因新发突变(de novo mutation)。在筛查到的众多孤独症相关新突变基因中,染色体结构域解旋酶DNA结合蛋白8(chromodomain helicase DNA-binding protein 8,CHD8)突变频率最高,是一个重要的孤独症候选致病基因。CHD8与p53、β-catenin等转录因子结合,具有复杂的转录调控作用。孤独症致病基因的发现为孤独症的诊断和治疗提供了分子靶标。展开更多
目的探讨染色体结构域解旋酶DNA结合蛋白8(chromodomain helicase DNA-binding protein 8,CHD8)与乙肝相关性肝癌(hepatocellular carcinoma,HCC)的临床病理学特征及术后肿瘤复发的相关性。方法回顾性分析2007年1月—2012年6月期间,解...目的探讨染色体结构域解旋酶DNA结合蛋白8(chromodomain helicase DNA-binding protein 8,CHD8)与乙肝相关性肝癌(hepatocellular carcinoma,HCC)的临床病理学特征及术后肿瘤复发的相关性。方法回顾性分析2007年1月—2012年6月期间,解放军总医院第三医学中心收治的251例肝移植术的乙肝相关性HCC患者的临床病理资料及长期随访资料,采用免疫组织化学法检测肝癌标本中的CHD8蛋白的表达,分析其与乙型肝炎e抗原(hepatitis B e antigen,HBeAg)、术后复发、转移等临床病理指标的相关性。结果免疫组织化学结果显示CHD8在乙肝相关性肝癌组织中的表达低于癌旁组织(P=0.00),临床病理特征分析提示CHD8的表达与微卫星灶(P=0.00)、血管侵犯(P=0.00)、除肝及肺外其他部位转移(P=0.00)明显相关,并与HBe Ag(P=0.04)、术后复发(P=0.01)、肺转移(P=0.04)具有相关性。结论 CHD8基因的表达与乙肝相关性HCC肝移植术后肿瘤转移复发相关,可能作为肝移植术后肿瘤复发转移的潜在标志物。展开更多
CHD8 is a candidate gene for autism spectrum disorders and neurological development delay.It has been reported to be essential for neurogenesis in the cerebral cortex,but the function of CHD8 in cerebellum has not bee...CHD8 is a candidate gene for autism spectrum disorders and neurological development delay.It has been reported to be essential for neurogenesis in the cerebral cortex,but the function of CHD8 in cerebellum has not been comprehensively investigated.The potential relationship of cerebellum dysplasia with psychiatric disorders in patients with CHD8 mutations is still not clear.In this study,we establish different conditional knockout mouse models to investigate the roles of CHD8 in cerebellar development.Mice with neural stem cell-specific Chd8 deletion exhibit significant reduction of cerebellum volume and no layering structure is detected.Genetic deletion of Chd8 in cerebellar granule neuron progenitors(GNPs)leads to cerebellar hypoplasia,absent of proliferation layer and ectopic of Purkinje neuron.However,no substantial cerebellar dysplasia is detected in mice with Purkinje neuron-or oligodendrocyte-specific Chd8 ablation.Single-cell RNA sequencing indicates that ribosome-related genes and pathways are most significantly disrupted in GNPs,indicating the potential mechanism.Importantly,in addition to the ataxia phenotype,mice with GNPspecific Chd8 ablation present a neuropsychiatric phenotype in three-chamber and light/dark tests.Taken together,our results provide insights not only into the function of CHD8 in cerebellar development,but also the pathogenesis of neuropsychiatric disorders in patients with CHD8 mutations.展开更多
文摘孤独症(即自闭症谱系障碍)是最常见的儿童中枢神经系统发育紊乱疾病。目前尚无特效治疗药物。最新的突破性进展是通过外显子组测序发现了一批与孤独症相关的单基因新发突变(de novo mutation)。在筛查到的众多孤独症相关新突变基因中,染色体结构域解旋酶DNA结合蛋白8(chromodomain helicase DNA-binding protein 8,CHD8)突变频率最高,是一个重要的孤独症候选致病基因。CHD8与p53、β-catenin等转录因子结合,具有复杂的转录调控作用。孤独症致病基因的发现为孤独症的诊断和治疗提供了分子靶标。
文摘目的探讨染色体结构域解旋酶DNA结合蛋白8(chromodomain helicase DNA-binding protein 8,CHD8)与乙肝相关性肝癌(hepatocellular carcinoma,HCC)的临床病理学特征及术后肿瘤复发的相关性。方法回顾性分析2007年1月—2012年6月期间,解放军总医院第三医学中心收治的251例肝移植术的乙肝相关性HCC患者的临床病理资料及长期随访资料,采用免疫组织化学法检测肝癌标本中的CHD8蛋白的表达,分析其与乙型肝炎e抗原(hepatitis B e antigen,HBeAg)、术后复发、转移等临床病理指标的相关性。结果免疫组织化学结果显示CHD8在乙肝相关性肝癌组织中的表达低于癌旁组织(P=0.00),临床病理特征分析提示CHD8的表达与微卫星灶(P=0.00)、血管侵犯(P=0.00)、除肝及肺外其他部位转移(P=0.00)明显相关,并与HBe Ag(P=0.04)、术后复发(P=0.01)、肺转移(P=0.04)具有相关性。结论 CHD8基因的表达与乙肝相关性HCC肝移植术后肿瘤转移复发相关,可能作为肝移植术后肿瘤复发转移的潜在标志物。
基金support by grants from the Science and Technology Commission of Shanghai Municipality(19411964400,20ZR1408400)National Natural Science Foundation of China(81741034,81720108018)+1 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01,2018SHZDZX05)ZJLab。
文摘CHD8 is a candidate gene for autism spectrum disorders and neurological development delay.It has been reported to be essential for neurogenesis in the cerebral cortex,but the function of CHD8 in cerebellum has not been comprehensively investigated.The potential relationship of cerebellum dysplasia with psychiatric disorders in patients with CHD8 mutations is still not clear.In this study,we establish different conditional knockout mouse models to investigate the roles of CHD8 in cerebellar development.Mice with neural stem cell-specific Chd8 deletion exhibit significant reduction of cerebellum volume and no layering structure is detected.Genetic deletion of Chd8 in cerebellar granule neuron progenitors(GNPs)leads to cerebellar hypoplasia,absent of proliferation layer and ectopic of Purkinje neuron.However,no substantial cerebellar dysplasia is detected in mice with Purkinje neuron-or oligodendrocyte-specific Chd8 ablation.Single-cell RNA sequencing indicates that ribosome-related genes and pathways are most significantly disrupted in GNPs,indicating the potential mechanism.Importantly,in addition to the ataxia phenotype,mice with GNPspecific Chd8 ablation present a neuropsychiatric phenotype in three-chamber and light/dark tests.Taken together,our results provide insights not only into the function of CHD8 in cerebellar development,but also the pathogenesis of neuropsychiatric disorders in patients with CHD8 mutations.
