Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics

被引:28
作者
Engblom, Camilla [1 ]
Thrane, Kim [2 ]
Lin, Qirong [1 ]
Andersson, Alma [2 ]
Toosi, Hosein [3 ]
Chen, Xinsong [4 ]
Steiner, Embla [1 ]
Lu, Chang [5 ,6 ]
Mantovani, Giulia [1 ]
Hagemann-Jensen, Michael [1 ]
Saarenpaa, Sami [2 ]
Jangard, Mattias [7 ,8 ]
Saez-Rodriguez, Julio [5 ,6 ]
Michaelsson, Jakob [9 ]
Hartman, Johan [4 ,10 ]
Lagergren, Jens [3 ]
Mold, Jeff E. [1 ]
Lundeberg, Joakim [2 ]
Frisen, Jonas [1 ]
机构
[1] Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden
[2] KTH Royal Inst Technol, Dept Gene Technol, SciLifeLab, Stockholm, Sweden
[3] KTH Royal Inst Technol, SciLifeLab, Computat Sci & Technol Dept, Stockholm, Sweden
[4] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden
[5] Heidelberg Univ, Fac Med, Heidelberg, Germany
[6] Heidelberg Univ Hosp, Inst Computat Biomed, Heidelberg, Germany
[7] Sophiahemmet Univ, ENT Unit, Res Lab, Stockholm, Sweden
[8] Sophiahemmet Hosp, Stockholm, Sweden
[9] Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden
[10] Karolinska Univ Hosp, Dept Clin Pathol & Canc Diagnost, Stockholm, Sweden
基金
欧盟地平线“2020”;
关键词
GERMINAL-CENTERS; DIVERSITY; TOOLKIT;
D O I
10.1126/science.adf8486
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed spatial transcriptomics of variable, diversity, and joining (VDJ) sequences (Spatial VDJ), a method that maps B cell and T cell receptor sequences in human tissue sections. Spatial VDJ captures lymphocyte clones that match canonical B and T cell distributions and amplifies clonal sequences confirmed by orthogonal methods. We found spatial congruency between paired receptor chains, developed a computational framework to predict receptor pairs, and linked the expansion of distinct B cell clones to different tumor-associated gene expression programs. Spatial VDJ delineates B cell clonal diversity and lineage trajectories within their anatomical niche. Thus, Spatial VDJ captures lymphocyte spatial clonal architecture across tissues, providing a platform to harness clonal sequences for therapy.
引用
收藏
页码:1137 / +
页数:17
相关论文
共 57 条
  • [1] Andersson A., 2021, Cell type enrichment within spatial regions
  • [2] Andersson A, 2022, star-repair
  • [3] Andersson A, 2021, NAT COMMUN, V12, DOI [10.1038/s41467-021-26271-2, 10.5281/ZENODO.3957256]
  • [4] Single-cell and spatial transcriptomics enables probabilistic inference of cell type topography
    Andersson, Alma
    Bergenstrahle, Joseph
    Asp, Michaela
    Bergenstrahle, Ludvig
    Jurek, Aleksandra
    Fernandez Navarro, Jose
    Lundeberg, Joakim
    [J]. COMMUNICATIONS BIOLOGY, 2020, 3 (01)
  • [5] [Anonymous], CD44 protein expression summary
  • [6] [Anonymous], Single cell type-SCGB2A2
  • [7] [Anonymous], PABPC1 protein expression summary
  • [8] [Anonymous], S100A8 protein expression summary
  • [9] Germinal centers in human lymph nodes contain reactivated memory B cells
    Bende, Richard J.
    van Maldegem, Febe
    Triesscheijn, Martijn
    Wormhoudt, Thera A. M.
    Guijt, Richard
    van Noesel, Carel J. M.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (11) : 2655 - 2665
  • [10] Seamless integration of image and molecular analysis for spatial transcriptomics workflows
    Bergenstrahle, Joseph
    Larsson, Ludvig
    Lundeberg, Joakim
    [J]. BMC GENOMICS, 2020, 21 (01)