Proximity labeling has emerged as a powerful strategy for interrogating cell-cell interactions. However, the nanometer-scale labeling radius impedes the use of current methods for indirect cell communications and makes recording cell spatial organization in tissue samples difficult. Here, we develop quinone methide–assisted identification of cell spatial organization (QMID), a chemical strategy with the labeling radius matching the cell dimension. The activating enzyme is installed on the surface of bait cells, which produces QM electrophiles that can diffuse across micrometers and label proximal prey cells independent of cell-cell contacts. In cell coculture, QMID reveals gene expression of macrophages that are regulated by spatial proximity to tumor cells. Furthermore, QMID enables labeling and isolation of proximal cells of CD4 + and CD8 + T cells in the mouse spleen, and subsequent single-cell RNA sequencing uncovers distinctive cell populations and gene expression patterns within the immune niches of specific T cell subtypes. QMID should facilitate dissecting cell spatial organization in various tissues.

中文翻译：

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用于记录小鼠组织中细胞空间组织的细胞级邻近标记

邻近标记已成为询问细胞间相互作用的强大策略。然而，纳米级标记半径阻碍了当前间接细胞通信方法的使用，并使组织样本中的细胞空间组织记录变得困难。在这里，我们开发了苯醌甲基化物辅助识别细胞空间组织 (QMID)，这是一种标记半径与细胞尺寸相匹配的化学策略。激活酶安装在诱饵细胞表面，产生 QM 亲电子试剂，可以扩散到微米级并标记近端猎物细胞，而不受细胞间接触的影响。在细胞共培养中，QMID 揭示了巨噬细胞的基因表达，这些表达受空间接近肿瘤细胞的调节。此外，QMID 能够标记和分离 CD4 的近端细胞+和CD8+小鼠脾脏中的 T 细胞和随后的单细胞 RNA 测序揭示了特定 T 细胞亚型免疫生态位内的独特细胞群和基因表达模式。QMID 应该有助于剖析各种组织中的细胞空间组织。