Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
Cells. 2023 Apr 15;12(8):1168. doi: 10.3390/cells12081168.
Down syndrome (DS) is a genetic disorder caused by an extra copy of chromosome 21 that presents developmental dysfunction and intellectual disability. To better understand the cellular changes associated with DS, we investigated the cell composition in blood, brain, and buccal swab samples from DS patients and controls using DNA methylation-based cell-type deconvolution. We used genome-scale DNA methylation data from Illumina HumanMethylation450k and HumanMethylationEPIC arrays to profile cell composition and trace fetal lineage cells in blood samples (DS N = 46; control N = 1469), brain samples from various regions (DS N = 71; control N = 101), and buccal swab samples (DS N = 10; control N = 10). In early development, the number of cells from the fetal lineage in the blood is drastically lower in DS patients (Δ = 17.5%), indicating an epigenetically dysregulated maturation process for DS patients. Across sample types, we observed significant alterations in relative cell-type proportions for DS subjects compared with the controls. Cell-type proportion alterations were present in samples from early development and adulthood. Our findings provide insight into DS cellular biology and suggest potential cellular interventional targets for DS.
唐氏综合征（DS）是一种由 21 号染色体额外拷贝引起的遗传疾病，表现为发育功能障碍和智力残疾。为了更好地了解与 DS 相关的细胞变化，我们使用基于 DNA 甲基化的细胞类型去卷积技术，研究了 DS 患者和对照者的血液、大脑和口腔拭子样本中的细胞组成。我们使用来自 Illumina HumanMethylation450k 和 HumanMethylationEPIC 阵列的全基因组 DNA 甲基化数据来分析血液样本（DS N = 46；对照 N = 1469）、来自不同区域的大脑样本（DS N = 71；对照 N = 101）和口腔拭子样本（DS N = 10；对照 N = 10）中的细胞组成和追踪胎儿谱系细胞。在早期发育中，DS 患者血液中的胎儿谱系细胞数量明显减少（Δ = 17.5%），这表明 DS 患者的成熟过程存在表观遗传失调。与对照者相比，我们在各种样本类型中观察到 DS 受试者的相对细胞类型比例发生了显著变化。细胞类型比例的改变存在于早期发育和成年期的样本中。我们的研究结果为 DS 的细胞生物学提供了深入的了解，并为 DS 提供了潜在的细胞干预靶点。
