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中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2023, Vol. 13 ›› Issue (03) : 159 -166. doi: 10.3877/cma.j.issn.2095-1221.2023.03.005

论著

衰弱与非衰弱高龄老人外周血单个核细胞单细胞转录组特征差异分析
曾静, 范皎, 史镜琪, 刘静, 李春霖, 徐国纲, 李天志†()   
  1. 100853　北京，解放军总医院第二医学中心内分泌科；100853　北京，国家老年疾病临床医学研究中心
    100853　北京，解放军总医院第二医学中心老年医学研究所；100853　北京，国家老年疾病临床医学研究中心
    100853　北京，国家老年疾病临床医学研究中心；100853　北京，解放军总医院第二医学中心
  • 收稿日期:2023-03-16 出版日期:2023-06-01
  • 通信作者: 李天志
  • 基金资助:
    国家重点研发计划(2020YFC2002706)

The transcriptome characteristics of single cells in the peripheral blood mononuclear cells between frail and non-frail elderly

Jing Zeng, Jiao Fan, Jingqi Shi, jing Liu, Chunlin Li, Guogang Xu, Tianzhi Li†()   

  1. Department of Endocrinology, the Second Medical Center, Chinese PLA General Hospital, Beijing 100853, China; National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China
    Institute of Geriatrics, the Second Medical Center, Chinese PLA General Hospital, Beijing 100853, China; National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China
    National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China; The Second Medical Center, Chinese PLA General Hospital, Beijing 100853, China
  • Received:2023-03-16 Published:2023-06-01
  • Corresponding author: Tianzhi Li
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引用本文：

曾静, 范皎, 史镜琪, 刘静, 李春霖, 徐国纲, 李天志. 衰弱与非衰弱高龄老人外周血单个核细胞单细胞转录组特征差异分析[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(03): 159-166.

Jing Zeng, Jiao Fan, Jingqi Shi, jing Liu, Chunlin Li, Guogang Xu, Tianzhi Li. The transcriptome characteristics of single cells in the peripheral blood mononuclear cells between frail and non-frail elderly[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(03): 159-166.

目的

已有研究表明衰老和衰弱影响人体免疫细胞转录组异质性和变异性。本研究着重探寻不同衰弱状态下高龄老人外周血转录组特征差异。

方法

下载基因表达数据库（GEO）中的GSE157007数据集，分析衰弱与非衰弱高龄老人外周血单个核细胞分布、特征，对差异表达基因（DEGs）进行京都基因与基因组百科全书（KEGG）通路富集分析，并采用CellChat包分析细胞间的相互作用和通讯情况。

结果

与非衰弱组相比，衰弱组中T细胞、单核细胞总比例降低，自然杀伤（NK）细胞比例升高，B细胞比例相当。组间各细胞亚群DEGs存在差异，通路富集分析发现DEGs主要富集于抗原呈递、肿瘤坏死因子信号通路和趋化因子信号等通路。进一步细胞通讯分析显示衰弱组细胞间相互作用数目和强度均少于非衰弱组，组间细胞间相互作用的模式和信号通路不同。

结论

不同衰弱状态的高龄老人外周血单细胞转录组特征存在差异。

关键词: 衰弱, 老年, 单细胞测序, 细胞通讯, 外周血
Objective

Recent studies have found that aging and frailty affect transcriptome heterogeneity and variability. Based on the existing evidence, this study aims to explore the differences in the transcriptome characteristics of peripheral blood of older people under different frailty states.

Methods

The dataset (GSE157007) was downloaded from the Gene Expression Omnibus (GEO) . The distribution and characteristics of cells and the differentially expressed genes between frail and non-frail elderly were analyzed. The differentially expressed genes were performed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The interaction and communication between cells were also studied by CellChat package.

Results

Compared with the non-frail group, the proportion of T cells and monocytes in the frail group was reduced, while the ratio of natural killer cells was increased. No significant difference was found in the cluster of B cells. And there were significant differences in gene expression among cell clusters. KEGG pathway analysis showed that differentially expressed genes were mainly enriched in antigen presentation, Tumor necrosis factor signaling pathway, chemokine signaling pathways. Further analysis of cell communication showed that the number and intensity of interactions between cells of the frail group were less than those in the non-frail group, and frailty states might affect the mode and signaling pathway of interactions between cells.

Conclusion

Significant differences were observed in the transcriptome characteristics of single cells in older people with different frailty states.

Key words: Frailty, Older adults, Single cell sequencing, Cell communication, Peripheral blood
图1 高龄老人不同衰弱状态外周血单个核细胞构成注：a图为不同衰弱状态来源细胞分布；b图为各个细胞聚类和亚群数量及分布；c图为各个细胞聚类和亚群在不同衰弱组间占比
图2 标记基因在各细胞亚群中的高表达情况
图3 高龄老人不同衰弱状态下各个细胞亚群差异基因火山图注：a图为记忆CD4+ T；b图为其他T2细胞；c图为B细胞；d图为单核细胞I亚群；e图为NK2细胞亚群；f图为mDCs细胞
图4 高龄老人不同衰弱状态下各个细胞亚群差异基因KEGG富集图
图5 CellChat分析高龄老人不同衰弱状态的各个细胞亚群相互作用情况注：a图为细胞间相互作用数量和强度对比；b图为细胞间相互作用数量和强度差异热图
图6 不同衰弱状态部分差异信号通路网络图（边的宽度代表细胞间通讯概率值大小）
图7 不同衰弱状态下分泌细胞的输出和输入通讯模式分析注：a图为衰弱样本；b图为非衰弱样本；线条宽度代表该细胞群或信号通路对每个对应模式的重要程度
图8 高龄老人不同衰弱状态bulk RNA-seq差异表达基因火山图和GO富集图
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