Zhao Jindong, Fang Zhaohui
Department of Endocrinology Two, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.
Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.
Front Immunol. 2025 Jan 23;15:1501660. doi: 10.3389/fimmu.2024.1501660. eCollection 2024.
Type 2 diabetes mellitus (T2DM) is a disease that involves autoimmunity. However, how immune cells function in the peripheral blood remains unclear. Exploring T2DM biomarkers via single-cell RNA sequencing (scRNA-seq) could provide new insights into the underlying molecular mechanisms.
The clinical trial registration number is ChiCTR2100049613. In this study, we included three healthy participants and three T2DM patients. The observed clinical indicators included weight and fasting blood glucose (FBG), glycosylated haemoglobin A1c (HbA1c) and fasting insulin levels. Direct separation and purification of peripheral blood mononuclear cells (PBMCs) were performed via the Ficoll density gradient centrifugation method. Immune cell types were identified via scRNA-seq. The differentially expressed genes, biological functions, cell cycle dynamics, and correlations between blood glucose indicators and genes in different cell types were analysed.
There were differences between the healthy and T2DM groups in terms of FBG and HbA1c (p<0.05 or p<0.01). We profiled 13,591 cells and 3188 marker genes from PBMCs. B cells, T cells, monocytes, and NK cells were grouped into 4 subclusters from PBMCs. CD4+ T cells are mainly in the memory activation stage, and CD8+ T cells are effectors. Monocytes include mainly CD14+ monocytes and FCGR3A+ monocytes. There were 119 differentially expressed genes in T cells and 175 differentially expressed genes in monocytes. Gene set enrichment analysis revealed that the marker genes were enriched in HALLMARK_ INTERFERON_GAMMA_RESPONSE and HALLMARK_TNFA_SIGNALING_VIA_ NFKB. Moreover, TNFRSF1A was identified as the core gene involved in network interactions in T cells.
Our study provides a transcriptional map of immune cells from PBMCs and provides a framework for understanding the immune status and potential immune mechanisms of T2DM patients via scRNA-seq.
http://www.chictr.org.cn, identifier ChiCTR2100049613.
2型糖尿病（T2DM）是一种涉及自身免疫的疾病。然而，免疫细胞在外周血中的功能仍不清楚。通过单细胞RNA测序（scRNA-seq）探索T2DM生物标志物可为潜在分子机制提供新见解。
临床试验注册号为ChiCTR2100049613。在本研究中，我们纳入了三名健康参与者和三名T2DM患者。观察的临床指标包括体重、空腹血糖（FBG）、糖化血红蛋白A1c（HbA1c）和空腹胰岛素水平。通过Ficoll密度梯度离心法对外周血单个核细胞（PBMC）进行直接分离和纯化。通过scRNA-seq鉴定免疫细胞类型。分析了不同细胞类型中差异表达基因、生物学功能、细胞周期动态以及血糖指标与基因之间的相关性。
健康组和T2DM组在FBG和HbA1c方面存在差异（p<0.05或p<0.01）。我们对PBMC中的13591个细胞和3188个标记基因进行了分析。B细胞、T细胞、单核细胞和NK细胞从PBMC中被分为4个亚群。CD4+T细胞主要处于记忆激活阶段，CD8+T细胞为效应细胞。单核细胞主要包括CD14+单核细胞和FCGR3A+单核细胞。T细胞中有119个差异表达基因，单核细胞中有175个差异表达基因。基因集富集分析显示，标记基因在HALLMARK_ INTERFERON_GAMMA_RESPONSE和HALLMARK_TNFA_SIGNALING_VIA_ NFKB中富集。此外，TNFRSF1A被确定为T细胞网络相互作用中的核心基因。
我们的研究提供了PBMC免疫细胞的转录图谱，并通过scRNA-seq为理解T2DM患者的免疫状态和潜在免疫机制提供了一个框架。
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