维普中文期刊产品整合服务

Integrated analysis on transcriptome and behaviors defines HTT repeat-dependent network modules in Huntington's disease

查看全文 作　　者：Lulin [1,2]Huang;Li [2]Fang;Qian [2]Liu;Abolfazl Doostparast [2]Torshizi;Kai [2]Wang 高影响力作者 机构地区：[1]The Key Laboratory for Human Disease Gene Study of Sichuan Province,Department of Clinical Laboratory,Sichuan Provincial People's Hospital,School of Medicine,University of Electronic Science and Technology of China,Chengdu,Sichuan 610054,PR China;[2]Raymond G.Perelman Center for Cellular and Molecular Therapeutics,Children's Hospital of Philadelphia,Philadelphia,PA 19104,USA高影响力机构 出　　处：《Genes & Diseases》索引2022年第9卷第2期,共15页高影响力期刊 基　　金：This research was supported by the National Natural Science Foundation of China(No.81970839 and 81670895 to L.H.);the Department of Science and Technology of Sichuan Province,China(No.2021YFS0033 to L.H). 摘　　要：Huntington's disease(HD)is caused by a CAG repeat expansion in the huntingtin(HTT)gene.Knock-in mice carrying a CAG repeat-expanded Htt will develop HD phenotypes.Previous studies suggested dysregulated molecular networks in a CAG length genotype-and the age-dependent manner in brain tissues from knock-in mice carrying expanded Htt CAG repeats.Furthermore,a large-scale phenome analysis defined a behavioral signature for HD genotype in knock-in mice carrying expanded Htt CAG repeats.However,an integrated analysis correlating phenotype features with genotypes(CAG repeat expansions)was not conducted previously.In this study,we revealed the landscape of the behavioral features and gene expression correlations based on 445 mRNA samples and 445 microRNA samples,together with behavioral features(396 PhenoCube behaviors and 111 NeuroCube behaviors)in Htt CAG-knock-in mice.We identified 37 behavioral features that were significantly associated with CAG repeat length including the number of steps and hind limb stand duration.The behavioral features were associated with several gene coexpression groups involved in neuronal dysfunctions,which were also supported by the single-cell RNA sequencing data in the striatum and the spatial gene expression in the brain.We also identified 15 chemicals with significant responses for genes with enriched behavioral features,most of them are agonist or antagonist for dopamine receptors and serotonin receptors used for neurology/psychiatry.Our study provides further evidence that abnormal neuronal signal transduction in the striatum plays an important role in causing HD-related phenotypic behaviors and provided rich information for the further pharmacotherapeutic intervention possibility for HD. 关 键 词：BEHAVIORS CAG repeat Huntington’s disease Mice Single-cell RNA sequencing Small chemicals STRIATUM TRANSCRIPTOME
相关文献

参考文献(60)

引证文献(1)

网站首页 | 关于我们 | 联系我们 | 产品服务 | 客服中心 | 广告服务 | 版权声明 | 网站联盟 | 友情链接 | 售卡网点

版权所有© 渝B2-20050021-1　渝公网安备 50019002500403号　违法和不良信息举报中心

互联网出版许可证 新出网证(渝)字10号 全国400电话 - 免长途话费