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单细胞测序揭示心脏移植物中树突状细胞和B细胞的抗原提呈特性

朱越星, 陈超, 徐晔, 等. 单细胞测序揭示心脏移植物中树突状细胞和B细胞的抗原提呈特性[J]. 器官移植. doi: 10.3969/j.issn.1674-7445.2024115
引用本文: 朱越星, 陈超, 徐晔, 等. 单细胞测序揭示心脏移植物中树突状细胞和B细胞的抗原提呈特性[J]. 器官移植. doi: 10.3969/j.issn.1674-7445.2024115
Zhu Yuexing, Chen Chao, Xu Ye, et al. Single cell sequencing reveals the antigen presentation characteristics of dendritic cells and B cells in cardiac grafts[J]. ORGAN TRANSPLANTATION. doi: 10.3969/j.issn.1674-7445.2024115
Citation: Zhu Yuexing, Chen Chao, Xu Ye, et al. Single cell sequencing reveals the antigen presentation characteristics of dendritic cells and B cells in cardiac grafts[J]. ORGAN TRANSPLANTATION. doi: 10.3969/j.issn.1674-7445.2024115

单细胞测序揭示心脏移植物中树突状细胞和B细胞的抗原提呈特性

doi: 10.3969/j.issn.1674-7445.2024115
基金项目: 国家自然科学基金面上项目(82070776、82270796、82200849、82370761);湖南省科技创新领军人才计划项目(2022RC3071);湖南省自然科学基金项目(2023JJ40872);中南大学高等教育教学改革项目(2023jy110)
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    作者简介:
    通讯作者:

    代贺龙(OCRID 0000-0002-0696-3081),博士,副研究员,研究方向为器官移植、移植免疫,Email:helong68888@163.com

  • 中图分类号: R617, R392.12

Single cell sequencing reveals the antigen presentation characteristics of dendritic cells and B cells in cardiac grafts

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  • 摘要:   目的  探讨心脏移植物中树突状细胞(DC)和B细胞的抗原提呈特性。  方法  将BALB/c小鼠的心脏移植到C57BL/6J小鼠腹腔内,术后5 d(急性排斥反应早期)提取并流式分选心脏移植物中的CD45+细胞,进行单细胞RNA测序。以心脏移植物中的DC和B细胞的亚群为主要对象,通过生物信息学分析和流式细胞术,研究其在心脏移植后变化趋势、抗原提呈能力及其与T细胞之间的胞间通讯情况。采用基因本体(GO)功能富集差异分析佐证细胞亚群特异性功能和细胞亚群注释可信度。  结果  生发中心样B细胞(GC-L B)是急性排斥反应期心脏移植物中增幅最大、比例高达87%的B细胞亚群,经典DC(cDC)2是心脏移植急性排斥期间唯一大量增多的DC亚群,占44%,是心脏移植后与T细胞的胞间通讯中占据最高通讯强度的DC亚群;单核样DC(moDC)与记忆性B细胞(MBC)是未心脏移植中T细胞输入信号的主要发出者,而在心脏移植后急性排斥反应期中,转变为cDC2与GC-L B;其中MBC与GC-L B分别是心脏移植前后的主要T细胞输入信号来源。  结论  在未移植心脏和移植心脏指向T细胞的胞间通讯中,与DC相比,B细胞均占据更高的通讯数量和权重,推测在心脏移植急性排斥反应早期,B细胞的抗原提呈活动比DC更加活跃,强度更大。

     

  • 图  1  小鼠未移植心脏及心脏移植物中B细胞免疫特征

    注:A图为4种B细胞亚型可视化UMAP图;B图为NH组和HTx组4种B细胞亚型数量;C图为Marker基因表达散点UMAP图,横纵坐标代表样本点在低维空间的相对位置关系,颜色深浅代表基因平均表达量高低;D图为代表性差异表达基因小提琴图。

    Figure  1.  B cell immune characteristics in non-transplanted hearts and heart grafts of mice

    图  2  小鼠心脏移植前后DC、B细胞及相应脾脏B细胞流式分析

    注:A图为心脏中B细胞流式图(B220+)及统计分析;B图为脾脏中B细胞流式图(CD19+)及统计分析;C图为DC流式图(MHC Ⅱ+、CD11c+)及统计分析。与NH组比较,aP<0.05。

    Figure  2.  Flow analysis of DC and B cells and corresponding spleen B cells before and after heart transplantation in mice

    图  3  小鼠未移植心脏及心脏移植物中DC免疫特征

    注:A图为4种DC亚型可视化UMAP图;B图我为4种DC亚型数量;C图为Marker基因表达散点UMAP图,横纵坐标代表样本点在低维空间的相对位置关系,颜色深浅代表基因平均表达量高低;D图为代表性差异表达基因小提琴图。

    Figure  3.  DC immune characteristics in non-transplanted hearts and heart grafts of mice

    图  4  小鼠心脏DC、B细胞与T细胞胞间交流分析

    注:A图为B细胞与T细胞之间胞间通讯的数量和权重可视化图;B图为DC与T细胞之间胞间通讯的数量和权重可视化图;C图为合并DC与B细胞,比对NH组与HTx组DC、B细胞与T细胞之间通讯强度的变化。

    Figure  4.  Analysis of intercellular communication among DC, B cells and T cells in mouse hearts

    图  5  CXCL信号通路在小鼠未移植心脏中DC、B细胞与T细胞之间的胞间通讯分析

    注:A图为DC、B细胞与T细胞输入、输出信号分析热图;B图为CXCL信号通路通讯弦图(指向T细胞);C图为CXCL信号通路通讯角色分析热图;D图为CXCL信号通路中受配体贡献度分析;E图为CXCL信号通路相关基因表达水平小提琴图。

    Figure  5.  Analysis of intercellular communication between DC, B cells and T cells of CXCL signaling pathway in non-transplanted mouse hearts

    图  6  CXCL信号通路在小鼠心脏移植急性排斥反应早期DC、B细胞与T细胞之间的胞间通讯分析

    注:A图为DC、B细胞与T细胞输入、输出信号分析热图;B图为CXCL信号通路通讯弦图(指向T细胞);C图为CXCL信号通路通讯角色分析热图;D图CXCL信号通路中受配体贡献度分析;E图为CXCL信号通路相关基因表达水平小提琴图。

    Figure  6.  Analysis of intracellular communication among DC, B cells and T cells by CXCL signaling pathway in the early stage of acute rejection of mouse heart transplantation

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  • 收稿日期:  2024-04-23
  • 网络出版日期:  2024-07-08

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