山东大学耳鼻喉眼学报 ›› 2022, Vol. 37 ›› Issue (6): 118-125.doi: 10.6040/j.issn.1673-3770.0.2022.109

• 临床研究 • 上一篇    

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

杨颖超,王圣明,刘峰,苏开明   

  1. 上海交通大学医学院附属第六人民医院 耳鼻咽喉头颈外科/上海交通大学 耳鼻咽喉科研究所/上海市睡眠呼吸障碍疾病重点实验室, 上海 200233
  • 发布日期:2023-12-15
  • 通讯作者: 苏开明. E-mail:021china@sina.com
  • 基金资助:
    国家自然科学基金项目(81974142)

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

YANG Yingchao, WANG Shengming, LIU Feng, SU Kaiming   

  1. Department of Otorhinolaryngology & Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital/Otolaryngological Institute, Shanghai Jiao Tong University/Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai 200233, China
  • Published:2023-12-15

摘要: 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。

关键词: 单细胞转录组测序, 滤泡树突状细胞, 腺样体肥大, 生物信息学分析, 发育路径

Abstract: 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.

Key words: Single-cell transcriptomic analysis, Follicular dendritic cells, Adenoid hypertrophy, Bioinformatic analysis, developmental trajectory

中图分类号: 

  • R765.21
[1] Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19[J]. Cell, 2021, 184(4): 861-880. doi:10.1016/j.cell.2021.01.007
[2] Tangye SG, Burnett DL, Bull RA. Getting to the(germinal)center of humoral immune responses to SARS-CoV-2[J]. Cell, 2022, 185(6): 945-948. doi:10.1016/j.cell.2022.02.018
[3] 刘燕, 魏萍, 寇巍, 等. 儿童腺样体肥大与耳鼻咽喉科常见疾病关系的研究进展[J]. 山东大学耳鼻喉眼学报, 2019, 33(4): 149-154. doi: 10.6040/j.issn.1673-3770.0.2018.266 LIU Yan, WEI Ping, KOU Wei, et al. Research of the relationship between adenoid hypertrophy and the common diseases of pediatric otolaryngology[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(4): 149-154. doi: 10.6040/j.issn.1673-3770.0.2018.266
[4] Mitchell J, Abbot A. Ultrastructure of the antigen-retaining Reticulum of lymph node follicles as shown by high-resolution autoradiography[J]. Nature, 1965, 208(5009): 500-502. doi:10.1038/208500b0
[5] Kosco MH, Pflugfelder E, Gray D. Follicular dendritic cell-dependent adhesion and proliferation of B cells in vitro[J]. J Immunol, 1992, 148(8): 2331-2339
[6] 蔡智, 郑世信, 高重阳. 扁桃体滤泡树突状细胞肉瘤1例及文献复习[J]. 山东大学耳鼻喉眼学报, 2012, 26(1): 55-57. doi: 10.6040/j.issn.1673-3770.2012.01.019 CAI Zhi, ZHENG Shixin, GAO Chongyang. Follicular dendritic cell sarcoma of tonsils: a case report and review[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2012, 26(1): 55-57. doi: 10.6040/j.issn.1673-3770.2012.01.019
[7] Cyster JG, Ansel KM, Reif K, et al. Follicular stromal cells and lymphocyte homing to follicles[J]. Immunol Rev, 2000, 176: 181-193. doi:10.1034/j.1600-065x.2000.00618.x
[8] Krautler NJ, Kana V, Kranich J, et al. Follicular dendritic cells emerge from ubiquitous perivascular precursors[J]. Cell, 2012, 150(1): 194-206. doi:10.1016/j.cell.2012.05.032
[9] Ware CF. Network communications: lymphotoxins, light, and TNF[J]. Annu Rev Immunol, 2005, 23: 787-819. doi:10.1146/annurev.immunol.23.021704.115719
[10] Elsner RA, Shlomchik MJ. Germinal center and extrafollicular B cell responses in vaccination, immunity, and autoimmunity[J]. Immunity, 2020, 53(6): 1136-1150. doi:10.1016/j.immuni.2020.11.006
[11] Usui K, Honda SI, Yoshizawa Y, et al. Isolation and characterization of naïve follicular dendritic cells[J]. Mol Immunol, 2012, 50(3): 172-176. doi:10.1016/j.molimm.2011.11.010
[12] Garis M, Garrett-Sinha LA. Notch signaling in B cell immune responses[J]. Front Immunol, 2021, 11: 609324. doi:10.3389/fimmu.2020.609324
[13] Chae WJ, Bothwell ALM. Canonical and non-canonical Wnt signaling in immune cells[J]. Trends Immunol, 2018, 39(10): 830-847. doi:10.1016/j.it.2018.08.006
[14] Sacedón R, Díez B, Nuñez V, et al. Sonic hedgehog is produced by follicular dendritic cells and protects germinal center B cells from apoptosis[J]. J Immunol, 2005, 174(3): 1456-1461. doi:10.4049/jimmunol.174.3.1456
[15] Lorenzi L, Döring C, Rausch T, et al. Identification of novel follicular dendritic cell sarcoma markers, FDCSP and SRGN, by whole transcriptome sequencing[J]. Oncotarget, 2017, 8(10): 16463-16472. doi:10.18632/oncotarget.14864
[16] Marshall AJ, Du Q, Draves KE, et al. FDC-SP, a novel secreted protein expressed by follicular dendritic cells[J]. J Immunol, 2002, 169(5): 2381-2389. doi:10.4049/jimmunol.169.5.2381
[17] Kranich J, Krautler NJ, Heinen E, et al. Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8[J]. J Exp Med, 2008, 205(6): 1293-1302. doi:10.1084/jem.20071019
[18] Suzuki K, Maruya M, Kawamoto S, et al. The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut[J]. Immunity, 2010, 33(1): 71-83. doi:10.1016/j.immuni.2010.07.003
[19] Rodda LB, Lu E, Bennett ML, et al. Single-cell RNA sequencing of lymph node stromal cells reveals niche-associated heterogeneity[J]. Immunity, 2018, 48(5): 1014-1028.e6. doi:10.1016/j.immuni.2018.04.006
[20] Hong R, Koga Y, Bandyadka S, et al. Comprehensive generation, visualization, and reporting of quality control metrics for single-cell RNA sequencing data[J]. Nat Commun, 2022, 13(1): 1688. doi:10.1038/s41467-022-29212-9
[21] Stuart T, Butler A, Hoffman P, et al. Comprehensive integration of single-cell data[J]. Cell, 2019, 177(7): 1888-1902. doi:10.1016/j.cell.2019.05.031
[22] Hao Y, Hao S, Andersen-Nissen E, et al. Integrated analysis of multimodal single-cell data[J]. Cell, 2021, 184(13): 3573-3587. doi:10.1016/j.cell.2021.04.048
[23] Korsunsky I, Millard N, Fan J, et al. Fast, sensitive and accurate integration of single-cell data with Harmony[J]. Nat Methods, 2019, 16(12): 1289-1296. doi:10.1038/s41592-019-0619-0
[24] Wu T, Hu E, Xu S, et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data[J]. Innovation(Camb), 2021, 2(3): 100141. doi:10.1016/j.xinn.2021.100141
[25] Aibar S, González-Blas CB, Moerman T, et al. SCENIC: single-cell regulatory network inference and clustering[J]. Nat Methods, 2017, 14(11): 1083-1086. doi:10.1038/nmeth.4463
[26] Huynh-Thu VA, Geurts P. Unsupervised gene network inference with decision trees and random forests[J]. Methods Mol Biol, 2019, 1883: 195-215. doi:10.1007/978-1-4939-8882-2_8
[27] Allen CDC, Okada T, Cyster JG. Germinal-center organization and cellular dynamics[J]. Immunity, 2007, 27(2): 190-202. doi:10.1016/j.immuni.2007.07.009
[28] Bajénoff M, Egen JG, Koo LY, et al. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes[J]. Immunity, 2006, 25(6): 989-1001. doi:10.1016/j.immuni.2006.10.011
[29] Wilke G, Steinhauser G, Grün J, et al. In silico subtraction approach reveals a close lineage relationship between follicular dendritic cells and BP3(hi)stromal cells isolated from SCID mice[J]. Eur J Immunol, 2010, 40(8): 2165-2173. doi:10.1002/eji.200940202
[30] Lu J, Chatterjee M, Schmid H, et al. CXCL14 as an emerging immune and inflammatory modulator[J]. J Inflamm(Lond), 2016, 13: 1. doi:10.1186/s12950-015-0109-9
[31] Westrich JA, Vermeer DW, Colbert PL, et al. The multifarious roles of the chemokine CXCL14 in cancer progression and immune responses[J]. Mol Carcinog, 2020, 59(7): 794-806. doi:10.1002/mc.23188
[32] Morgan B, Sun L, Avitahl N, et al. Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation[J]. EMBO J, 1997, 16(8): 2004-2013. doi:10.1093/emboj/16.8.2004
[33] Areshkov PO, Avdieiev SS, Balynska OV, et al. Two closely related human members of chitinase-like family, CHI3L1 and CHI3L2, activate ERK1/2 in 293 and U373 cells but have the different influence on cell proliferation[J]. Int J Biol Sci, 2012, 8(1): 39-48. doi:10.7150/ijbs.8.39
[34] Huang Y, Du KL, Guo PY, et al. IL-16 regulates macrophage polarization as a target gene of mir-145-3p[J]. Mol Immunol, 2019, 107: 1-9. doi:10.1016/j.molimm.2018.12.027
[35] Ma J, Jiang T, Tan L, et al. TYROBP in Alzheimer's disease[J]. Mol Neurobiol, 2015, 51(2): 820-826. doi:10.1007/s12035-014-8811-9
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