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

来源：

SCIENCE | 2023年 / 382卷 / 6675期

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

页码：1137 / +

页数：17

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