研究人员开发了可变、多样性和连接（VDJ）序列的空间转录组学（空间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。空间VDJ捕获与典型B和T细胞分布相匹配的淋巴细胞克隆，并扩增经正交方法证实的克隆序列。
研究人员发现了配对受体链之间的空间一致性，开发了一个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。空间VDJ描绘了B细胞克隆多样性和在其解剖微环境的谱系轨迹。因此，空间VDJ捕获淋巴细胞跨组织的空间克隆结构，并为利用克隆序列进行治疗提供了平台。
据了解，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。
附：英文原文
Title: Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics
Author: Camilla Engblom, Kim Thrane, Qirong Lin, Alma Andersson, Hosein Toosi, Xinsong Chen, Embla Steiner, Chang Lu, Giulia Mantovani, Michael Hagemann-Jensen, Sami Saarenp, Mattias Jangard, Julio Saez-Rodriguez, Jakob Michalsson, Johan Hartman, Jens Lagergren, Jeff E. Mold, Joakim Lundeberg, Jonas Frisén
Issue&Volume: 2023-12-08
Abstract: 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.
DOI: adf8486
Source: https://www.science.org/doi/10.1126/science.adf8486