基于单细胞ATAC测序技术对18-三体综合征染色质开放性区域转录因子的分析  

Analysis of transcription factors in accessible open chromatin in the 18-trisomy syndrome based on single cell ATAC sequencing technique

作　　者：邱晓芬 汤冬娥 虞海燕 廖秋燕 胡芷洋[3] 周俊 赵鑫 何慧燕 梁灼健[3] 许承明 杨明 戴勇[1] Xiaofen Qiu;Dong’e Tang;Haiyan Yu;Qiuyan Liao;Zhiyang Hu;Jun Zhou;Xin Zhao;Huiyan He;Zhuojian Liang;Chengming Xu;Ming Yang;Yong Dai(College of Life Science,Guangxi Normal University,Guilin 541006,China;Guangxi Key Laboratory of Metabolic Diseases Research,Department of Clinical Laboratory of Guilin No.924 Hospital,Guilin 541002,China;Clinical Medical Research Center,Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine,Shenzhen Engineering Research Center of Autoimmune Disease,The Second Clinical Medical College of Jinan University,The First Affiliated Hospital of Southern University of Science and Technology,Shenzhen People’s Hospital,Shenzhen 518020,China)

机构地区：[1]广西师范大学生命科学学院,桂林541006 [2]中国人民解放军联勤保障部队第924医院妇幼与生殖中心广西代谢性疾病研究重点实验室,桂林541002 [3]暨南大学第二临床医学院和南方科技大学第一附属医学院(深圳市人民医院)临床医学研究中心,广东省自身免疫性疾病精准医疗工程技术研究中心,深圳市自身免疫病工程研究中心,深圳518020

出　　处：《遗传》2021年第1期74-83,I0002-I0006,共15页Hereditas（Beijing)

基　　金：广东省科技计划项目(编号:2017B020209001);深圳市科技计划项目(编号:GJHZ20180413181714541);广西重点实验室建设项目(编号:20-065-76);桂林市科学研究与技术开发计划项目(编号:2016012702-1)资助。

摘　　要：18-三体综合征是常见的常染色体非整倍体疾病之一,长期以来人们对18-三体综合征疾病的临床表型(如智力障碍、心脏、肾脏异常等)发生及发展相关的基因调控知之甚少。为探索影响该疾病表型的调控因子,本研究利用单细胞ATAC测序技术,对18-三体综合征和对照组的脐带血单个核细胞的开放性染色质区域的转录因子进行分析。捕获11,611个细胞构建的单细胞文库鉴定得到7种主要免疫细胞群,细胞数量统计的结果提示18-三体综合征的免疫系统异常。通过分析开放性染色质区域,筛选得到14个转录因子(P<0.05,|FC|>1.2)。采用实时荧光定量PCR验证其中4个转录因子(TEAD1、TEAD2、TEAD4、Twist2)的相对表达量的结果符合预期。上述研究结果表明这4个转录因子可能与18-三体综合征患者心脏和骨骼发育的异常相关,为18-三体综合征表型的发生及发展的机制研究提供候选分子。Trisomy 18 syndrome is one of the most common autosomal aneuploidy disorders.Little is known about the genetic regulation leading to the clinical phenotypes associated with the occurrence and development of trisomy 18 syndrome disorders(e.g.,mental retardation,cardiac and renal abnormalities).To explore the regulatory factors that influence the phenotypes of the disease,this study used single-cell ATAC sequencing to analyze transcription factors in the accessibility chromatin regions of the single-nucleus cells of the cord blood from 18-trisomy syndrome and control subjects.A single-cell library constructed by capturing 11,611 cells identified seven major immune cell populations,and the results of cell number statistics suggested the presence of abnormalities in the immune system of 18-trisomy syndrome patients.Fourteen transcription factors(P<0.05,|FC|>1.2)were identified by analyzed accessibility chromatin regions.The relative expression levels of four of these transcription factors(TEAD1,TEAD2,TEAD4,Twist2)were confirmed using real-time quantitative fluorescence PCR.In conjunction with information from the literature,this study suggests that these four transcription factors may be associated with abnormalities in cardiac and skeletal development in patients with the 18-trisomy syndrome,thereby providing candidate molecules for mechanistic studies on the occurrence and development of the 18-trisomy syndrome phenotypes.

关 键 词：18-三体综合征 单个核细胞 单细胞ATAC测序 转录调控 转录因子 

分 类 号：R596.1[医药卫生—内科学]