儿童肥大腺样体滤泡树突状细胞精细分群及发育路径分析

Sophisticated clustering and developmental trajectory of pediatric hypertrophic adenoid follicular dendritic cells

目的 探讨儿童肥大腺样体组织滤泡树突状细胞(follicular dendritic cells, FDCs)的基因表达特征、精细分群、发育路径及转录调控网络。方法 采用单细胞转录组测序技术结合生物信息学分析手段,明确儿童肥大腺样体组织FDCs的基因表达特征及亚群分群信息;通过KEGG、GO、irGSEA等基因功能富集分析方法,阐述不同FDCs亚群生物学功能;利用拟时序分析,探索FDCs细胞亚群间的发育关系;运用SCENIC分析方法描绘不同FDCs亚群的转录调控网络。结果 共获得6个FDCs亚群,功能富集结果显示它们具有不同的功能;拟时序分析结果显示各亚群的发育分化轨迹起始于CXCL14^(+)APOD^(+)FDCs与SLCO2B1^(+)PAPPA^(+)FDCs;转录因子调控网络的分析结果提示FDCs的SCENIC分群与Seurat分群并非完全重合,多组间存在较大比例的交叉。结论 儿童肥大腺样体组织内包含多个FDCs亚群,具有多种功能,存在连续的发育分化关系,部分亚群受到相同的转录因子网络的调控。

Objective To clarify transcriptome characteristics,sophisticated clustering,developmental trajectory,and transcriptional regulatory network of pediatric hypertrophic adenoid follicular dendritic cells(FDCs).Methods The gene expression characteristics and subpopulation features of FDCs in pediatric hypertrophic adenoids were obtained by single-cell transcriptome sequencing and bioinformatics analysis,while the biological functions of different FDCs subpopulations were determined via enrichment analysis using KEGG,GO and irGSEA.The developmental trajectory among FDCs subpopulations was determined through pseudotime analysis,and the transcriptional regulatory networks of different FDCs subpopulations were determined using SCENIC.Results Six FDCs subpopulations were determined;each with different functions on enrichment analysis.The developmental trajectory began with CXCL14^(+)APOD^(+)FDCs and SLCO2B1^(+)PAPPA^(+)FDCs.Analysis of transcriptional regulatory networks indicated that FDCs subpopulations determined using SCENIC did not completely overlap with those determined using Seurat.There was a considerable proportion of crossover between different subpopulations.Conclusion Pediatric hypertrophic adenoids comprise different FDCs subpopulations that have multiple functions.There is a continuous developmental trajectory among them.In addition,some subpopulations accept regulations from the same transcriptional regulatory networks.