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.