期刊文献+

基于单细胞RNA测序解析人与小鼠睾丸中SARS-CoV-2相关受体的时空表达特征

Single-cell RNA sequencing reveals the spatio-temporal expression profile of SARS-CoV-2 related receptor in human and mouse testes
下载PDF
导出
摘要 目的·基于单细胞RNA测序(single-cell RNA sequencing,scRNA-Seq),分析严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)受体血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)在人和小鼠睾丸中的时空表达特征。方法·收集生理性各发育阶段的人睾丸组织10例和C57BL/6小鼠睾丸组织9例,用酶消化成单细胞悬液后经scRNA-Seq标准处理程序得到细胞-基因表达矩阵。经过质量控制、数据标准化、批次效应处理和聚类降维后,利用已知的睾丸细胞标志物注释各群细胞,以明确在发育的不同阶段中人和小鼠睾丸中ACE2表达模式和差异。结果·鉴定出人和小鼠均有的睾丸细胞亚群9个,包括3群生殖细胞(精原细胞、精母细胞和精子细胞/精子)和6群体细胞(Sertoli细胞、巨噬细胞、血管平滑肌细胞、内皮细胞、Leydig细胞和管周肌样细胞)。从空间分布来看,在成人睾丸中,ACE2主要表达于Sertoli细胞,在Leydig细胞、管周肌样细胞和生殖细胞也有表达。从时间尺度上看,人Sertoli细胞的ACE2转录丰度随着睾丸的发育而增加,青春期后Sertoli细胞中ACE2表达显著高于幼儿期和儿童期(P=0.000)。从小鼠睾丸发育各阶段来看,Ace2表达模式与人体均有显著不同。在5周龄成年C57BL/6小鼠睾丸中,Ace2的转录水平低且主要表达于血管平滑肌细胞(P=0.000),而Sertoli细胞中Ace2阳性细胞数则极少。结论·SARS-CoV-2可能主要通过Sertoli细胞感染人类睾丸,常规C57BL/6小鼠模型不适用于模拟SARS-CoV-2感染对人类睾丸的功能影响。 Objective·To analyze the spatio-temporal expression profile of angiotensin-converting enzyme 2(ACE2),the receptor of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),in human and mouse testes based on single-cell RNA sequencing(scRNA-Seq).Methods·Ten testicular tissues from humans and nine testicular tissues from C57BL/6 mice with normal developmental stages were collected and digested into single cell suspensions by enzyme,and then the cell-gene expression matrixes were obtained by scRNA-Seq standard processing procedures.After quality control,data standardization,batch effect processing,clustering,and dimensionality reduction,each subgroup of cells was annotated based on known testicular cell bio-markers to clarify the expression patterns and differences of ACE2 in human and mouse testes with normal developmental stages.Results·In this study,nine testicular cell subgroups found in human and mice were identified,including three subgroups of germ cells(spermatogonia,spermatocytes,and spermatids/sperm)and six subgroups of somatic cells(Sertoli cells,macrophages,vascular smooth muscle cells,endothelial cells,Leydig cells,and peritubular myoid cells).In terms of spatial distribution,ACE2 was predominantly expressed in human Sertoli cells in adult testes,and also expressed in Leydig cells,peritubular myoid cells,and germ cells.In terms of time scale,the transcription abundance of ACE2 in human Sertoli cells increased with the development of testis,and the expression level of ACE2 in Sertoli cells after puberty was significantly higher than that in infancy and childhood(P=0.000).Judging from the stages of mouse testicular development,the expression patterns of Ace2 were both significantly different from those in humans.In testis of the 5-week-old adult C57BL/6 mouse,the transcription level of Ace2 was low and it was mainly expressed in vascular smooth muscle cells(P=0.000),while the number of Ace2 positive cell in Sertoli cells was extremely low.Conclusion·SARS-CoV-2 may mainly infects human testis through Sertoli cells,and the conventional C57BL/6 mouse model is not suitable to simulate the effect of SARS-CoV-2 infection on human testicular function.
作者 罗嘉强 赵亮宇 姚晨成 朱子珏 邢晓宇 李朋 田汝辉 陈慧兴 孙杰 李铮 LUO Jia-qiang;ZHAO Liang-yu;YAO Chen-cheng;ZHU Zi-jue;XING Xiao-yu;LI Peng;TIAN Ru-hui;CHEN Hui-xing;SUN Jie;LI Zheng(Urologic Medical Center,Department of Andrology,Department of Assisted Reproductive Medicine,Shanghai General Hospital,Shanghai Jiao Tong University,Shanghai 200080,China;Center for Men's Health,Shanghai Key Lab of Reproductive Medicine,Institute of Urology,Shanghai Jiao Tong University,Shanghai 200080,China;Department of Urology,Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China)
出处 《上海交通大学学报(医学版)》 CAS CSCD 北大核心 2021年第4期421-426,共6页 Journal of Shanghai Jiao tong University:Medical Science
基金 国家重点研发计划(2017YFC1002003) 上海市科学技术委员会项目(17JC1420103)。
关键词 严重急性呼吸综合征冠状病毒2 单细胞RNA测序 血管紧张素转化酶2 病毒性睾丸炎 SERTOLI细胞 severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) single-cell RNA sequencing(scRNA-Seq) angiotensin-converting enzyme 2(ACE2) viral orchitis Sertoli cell
  • 相关文献

参考文献2

二级参考文献11

  • 1Dejucq N,Je'gou B.Viruses in the mammalian male genital tract and their effects on the reproductive system.Microbiol Mol Biol Rev,2001,65(2),208-231.
  • 2Shi X,Gong E,Gao D,et al.Severe acute respiratory syndrome associated coronavirus is detected in intestinal tissues of fatal cases.Am J Gastroenterol,2005,100(1):169-176.
  • 3Li W,Moore MJ,Vasilieva N,etal.Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.Nature,2003,426(6965):450-454.
  • 4Harmer D,Gilbert M,Borman R,et al.Quantitative mRNA expression profiling of ACE2,a novel homologue of angiotensin converting enzyme.FEBS,2002,532(1-2),107-110.
  • 5Tipnis SR,Hooper NM,Hyde R,et al.A human homolog of angiotensin-converting enzyme.J Biol Chem,2000,275 (43):33238-33243.
  • 6Donoghue M,Hsieh F,Baronas E,et al.A novel angiotensinconverting enzyme-related carboxypeptidase (ACE2) converts angiotensin Ⅰ to angiotensin 1-9.Circ Res,2000,87(5):1-9.
  • 7Ding Y,He L,Zhang Q,et al.Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients:implications for pathogenesis and virus transmission pathways.J Pathol,2004,203 (2):622-630.
  • 8Itoh M,Hiramine C,Tokunaga Y,et al.A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone.Ⅱ.Immunohistochemical findings of fully-developed inflammatory lesion.Autoimmunity,1991,10(2):89-97.
  • 9Kohno S,Munoz JA,Williams TM,et al.Immunopathology of murine experimental allergic orchitis.J Immunol,1983,130(6):2675-2682.
  • 10赵景民,周光德,孙艳玲,王松山,杨建法,孟二红,潘登,陆江阳,李玲,李进,辛绍杰,赵敏,陈菊梅,张玲霞.严重急性呼吸综合征肺外器官的病理学观察研究[J].解放军医学杂志,2003,28(6):480-481. 被引量:37

共引文献24

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部