Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
SciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden.
Science. 2023 Dec 8;382(6675):eadf8486. doi: 10.1126/science.adf8486.
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.
淋巴细胞克隆在组织内的空间分布对其发育、选择和扩增至关重要。我们开发了可变、多样性和连接(VDJ)序列的空间转录组学(Spatial VDJ),这是一种在人体组织切片中绘制 B 细胞和 T 细胞受体序列的方法。Spatial VDJ 捕获与经典 B 和 T 细胞分布相匹配的淋巴细胞克隆,并扩增通过正交方法确认的克隆序列。我们发现了配对受体链之间的空间一致性,开发了一种计算框架来预测受体对,并将不同 B 细胞克隆的扩增与不同的肿瘤相关基因表达程序联系起来。Spatial VDJ 描绘了 B 细胞克隆多样性及其在解剖学龛位中的谱系轨迹。因此,Spatial VDJ 捕获了淋巴细胞在整个组织中的空间克隆结构,为利用克隆序列进行治疗提供了一个平台。
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