21三体,或唐氏综合征(DS),是人类最常见的常染色体染色体非整倍性,导致多种发育障碍,尤其是个体的智力低下。另外的21号人类染色体(HSA21)的存在可以解释DS的病理表现。在这项研究中,我们分析了DS来源羊膜细胞与正常羊膜细胞相比的mRNA基因表达谱,旨在评估候选HSA21基因失调与DS发育表型之间的关系。差异表达基因(DEGs)包括1794个上调基因和1411个下调基因,主要参与细胞粘附,炎症,细胞增殖,因此可能在DS胎儿发育过程中诱导多发性发育不良中起重要作用。此外,STRING蛋白质网络研究表明,7个候选HSA21基因参与了基因本体论(GO)术语:细胞粘附和细胞外基质重塑(COL6A1,COL6A2,COL18A1,ADAMTS5,JAM2和POFUT2),炎症和病毒感染反应(MX1和MX2),组蛋白修饰和染色质重塑(NRIP1),甘油脂和甘油磷脂代谢(AGPAT3),线粒体功能(ATP5PF和ATP5PO),突触小泡内吞(ITSN1和SYNJ1)和淀粉样蛋白代谢(APP)。同时,GSEA富集鉴定了几种转录因子和miRNA,其可以靶向DS组中的基因表达。我们的研究建立了失调基因之间的联系,尤其是HSA21基因,和DS相关表型。多种途径和生物过程的改变可能导致DS发育障碍,为DS提供潜在的发病机制和治疗靶点。
Trisomy 21, or Down syndrome (DS), is the most frequent human autosomal chromosome aneuploidy, which leads to multiple developmental disorders, especially mental retardation in individuals. The presence of an additional human chromosome 21 (HSA21) could account for the pathological manifestations in DS. In this study, we analyzed the mRNA gene expression profile of DS-derived amniocytes compared with normal amniocytes, aiming to evaluate the relationship between candidate dysregulated HSA21 genes and DS developmental phenotypes. Differentially expressed genes (DEGs) included 1794 upregulated genes and 1411 downregulated genes, which are mainly involved in cell adhesion, inflammation, cell proliferation and thus may play an important role in inducing multiple dysplasia during DS fetal development. Furthermore, STRING protein network studies demonstrated 7 candidate HSA21 genes participated Gene Ontology (GO) terms: cell adhesion and extracellular matrix remodeling (COL6A1, COL6A2, COL18A1, ADAMTS5, JAM2, and POFUT2), inflammation and virus infection response (MX1 and MX2), histone modification and chromatin remodeling (NRIP1), glycerolipid and glycerophospholipid metabolism (AGPAT3), mitochondrial function (ATP5PF and ATP5PO), synaptic vesicle endocytosis (ITSN1 and SYNJ1) and amyloid metabolism (APP). Meanwhile, GSEA enrichment identified several transcription factors and miRNAs, which may target gene expression in the DS group. Our study established connections between dysregulated genes, especially HSA21 genes, and DS-associated phenotypes. The alteration of multiple pathways and biological processes may contribute to DS developmental disorders, providing potential pathogenesis and therapeutic targets for DS.