Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, 518020, People's Republic of China.
Guangxi Key Laboratory of Metabolic Diseases Research, Department of Clinical Laboratory of Guilin, No. 924 Hospital, 541002, Guilin, Guangxi, People's Republic of China.
Hum Genomics. 2021 Jun 30;15(1):40. doi: 10.1186/s40246-021-00338-z.
Trisomy 18 syndrome (Edwards syndrome, ES) is a type of aneuploidy caused by the presence of an extra chromosome 18. Aneuploidy is the leading cause of early pregnancy loss, intellectual disability, and multiple congenital anomalies. The research of trisomy 18 is progressing slowly, and the molecular characteristics of the disease mechanism and phenotype are still largely unclear.
In this study, we used the commercial Chromium platform (10× Genomics) to perform sc-ATAC-seq to measure chromatin accessibility in 11,611 single umbilical cord blood cells derived from one trisomy 18 syndrome patient and one healthy donor. We obtained 13 distinct major clusters of cells and identified them as 6 human umbilical cord blood mononuclear cell types using analysis tool. Compared with the NC group, the ES group had a lower ratio of T cells to NK cells, the ratio of monocytes/DC cell population did not change significantly, and the ratio of B cell nuclear progenitor and megakaryocyte erythroid cells was higher. The differential genes of ME-0 are enriched in Human T cell leukemia virus 1 infection pathway, and the differential peak genes of ME-1 are enriched in apopotosis pathway. We found that CCNB2 and MCM3 may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin.
We have identified 6 cell populations in cord blood. Disorder in megakaryocyte erythroid cells implicates trisomy 18 in perturbing fetal hematopoiesis. We identified a pathway in which the master differential regulatory pathway in the ME-0 cell population involves human T cell leukemia virus 1 infection, a pathway that is dysregulated in patients with trisomy 18 and which may increase the risk of leukemia in patients with trisomy 18. CCNB2 and MCM3 in progenitor may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin, may be related to chromosomal abnormalities in trisomy 18.
18 三体综合征（爱德华兹综合征，ES）是一种由额外的 18 号染色体引起的非整倍体。非整倍体是早期妊娠丢失、智力障碍和多种先天性异常的主要原因。18 三体的研究进展缓慢，疾病机制和表型的分子特征在很大程度上仍不清楚。
在这项研究中，我们使用商业的 Chromium 平台（10× Genomics）对 11611 个源自 1 例 18 三体综合征患者和 1 例健康供体的单个脐血单个核细胞进行 sc-ATAC-seq 以测量染色质可及性。我们获得了 13 个不同的主要细胞簇，并使用分析工具将其鉴定为 6 个人类脐血单核细胞类型。与 NC 组相比，ES 组 T 细胞与 NK 细胞的比例较低，单核细胞/DC 细胞群的比例没有明显变化，B 细胞核祖细胞和巨核细胞红细胞的比例较高。ME-0 的差异基因在人类 T 细胞白血病病毒 1 感染途径中富集，ME-1 的差异峰基因在细胞凋亡途径中富集。我们发现 CCNB2 和 MCM3 可能对 18 三体的发展至关重要。CCNB2 和 MCM3 已被报道为细胞周期和染色质的重要组成部分。
我们已经在脐血中鉴定出 6 种细胞群。巨核细胞红细胞紊乱提示 18 三体干扰胎儿造血。我们确定了一个途径，在 ME-0 细胞群中的主差异调节途径涉及人类 T 细胞白血病病毒 1 感染，该途径在 18 三体患者中失调，这可能增加 18 三体患者患白血病的风险。祖细胞中的 CCNB2 和 MCM3 可能对 18 三体的发展至关重要。CCNB2 和 MCM3 已被报道为细胞周期和染色质的重要组成部分，可能与 18 三体的染色体异常有关。
