Sex Differences in Coronary Artery Disease and Diabetes Revealed by scRNA-Seq and CITE-Seq of Human CD4+ T Cells.
Sex Differences in Coronary Artery Disease and Diabetes Revealed by scRNA-Seq and CITE-Seq of Human CD4+ T Cells.
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人类CD4+T细胞scRNA-SEQ和CITE-SEQ揭示冠心病和糖尿病的性别差异
DOI：
10.3390/ijms23179875
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发表时间：
2022-08-30
影响因子：
5.6
通讯作者：
Ley, Klaus
中科院分区：
文献类型：
--
作者：
Saigusa, Ryosuke;Vallejo, Jenifer;Gulati, Rishab;Suthahar, Sujit Silas Armstrong;Suryawanshi, Vasantika;Alimadadi, Ahmad;Makings, Jeffrey;Durant, Christopher P.;Freuchet, Antoine;Roy, Payel;Ghosheh, Yanal;Pandori, William;Pattarabanjird, Tanyaporn;Drago, Fabrizio;Taylor, Angela;McNamara, Coleen A.;Shemesh, Avishai;Lanier, Lewis L.;Hedrick, Catherine C.;Ley, Klaus
尽管几十年来人们都知道男性和糖尿病患者患冠状动脉疾病（CAD）的风险增加，但人们对这种关联的原因只了解了一部分。在涉及的免疫细胞中，最近的证据支持T细胞作为CAD的驱动和修饰剂的关键作用。CD4+ T细胞常见于动脉粥样硬化斑块。我们旨在通过CD4+ T细胞的单细胞RNA （scRNA-Seq）和抗体测序（CITE-Seq）了解CAD与性别和DM的关系。采用scRNA-Seq联合49种表面标记物（CITE-Seq）对61例接受心导管置入术的男性和女性的外周血单个核细胞（PBMCs）进行检测。使用Gensini评分对CAD严重程度进行量化，评分高于30分为CAD+，低于6分为CAD -。根据临床和人口学参数对四组进行匹配。为了测试性别和糖尿病如何改变细胞比例和基因表达，我们比较了匹配组的男性和女性，以及糖尿病和非糖尿病受试者。我们分析了16名女性和45名男性的41782个CD4+ T细胞转录组的性别差异，这些患者有和没有冠状动脉疾病，有和没有糖尿病。我们鉴定了16个CD4+ T细胞簇。CD4+效应记忆簇8 （CD4T8, CCR2+ Em）的细胞比例在CAD+中显著降低，尤其是在DM+参与者中。在女性参与者中，同样的CD4+ T细胞群CD4T8和其他两种CD4+ T细胞群显著减少。在CD4+ T细胞中，31个基因在CAD和DM中均表现出显著和协调的上调。DM基因信号部分添加到CAD基因信号中。我们得出结论：(1)CAD和DM在PBMC转录组中有明显的反映，(2)女性和男性之间存在显著差异，(3)糖尿病和非糖尿病受试者之间存在显著差异。
Despite the decades-old knowledge that males and people with diabetes mellitus (DM) are at increased risk for coronary artery disease (CAD), the reasons for this association are only partially understood. Among the immune cells involved, recent evidence supports a critical role of T cells as drivers and modifiers of CAD. CD4+ T cells are commonly found in atherosclerotic plaques. We aimed to understand the relationship of CAD with sex and DM by single-cell RNA (scRNA-Seq) and antibody sequencing (CITE-Seq) of CD4+ T cells. Peripheral blood mononuclear cells (PBMCs) of 61 men and women who underwent cardiac catheterization were interrogated by scRNA-Seq combined with 49 surface markers (CITE-Seq). CAD severity was quantified using Gensini scores, with scores above 30 considered CAD+ and below 6 considered CAD−. Four pairs of groups were matched for clinical and demographic parameters. To test how sex and DM changed cell proportions and gene expression, we compared matched groups of men and women, as well as diabetic and non-diabetic subjects. We analyzed 41,782 single CD4+ T cell transcriptomes for sex differences in 16 women and 45 men with and without coronary artery disease and with and without DM. We identified 16 clusters in CD4+ T cells. The proportion of cells in CD4+ effector memory cluster 8 (CD4T8, CCR2+ Em) was significantly decreased in CAD+, especially among DM+ participants. This same cluster, CD4T8, was significantly decreased in female participants, along with two other CD4+ T cell clusters. In CD4+ T cells, 31 genes showed significant and coordinated upregulation in both CAD and DM. The DM gene signature was partially additive to the CAD gene signature. We conclude that (1) CAD and DM are clearly reflected in PBMC transcriptomes, and (2) significant differences exist between women and men and (3) between subjects with DM and non-DM.
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