Dissecting cellular crosstalk by sequencing physically interacting cells
Dissecting cellular crosstalk by sequencing physically interacting cells
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DOI：
10.1038/s41587-020-0442-2
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发表时间：
2020-03-09
影响因子：
46.9
通讯作者：
Amit, Ido
中科院分区：
文献类型：
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作者：
Giladi, Amir;Cohen, Merav;Amit, Ido
PIC-seq通过对物理相互作用的细胞进行分选和测序来表征细胞串扰。相邻细胞之间的串扰是许多生物过程的基础，包括细胞信号传导、增殖和分化。目前的单细胞基因组技术在组织解离后单独分析每个细胞，丢失了细胞间相互作用的信息。在本研究中，我们提出了一种对物理相互作用细胞（PIC-seq）进行测序的方法，该方法将物理相互作用细胞（PIC）的细胞分选与单细胞RNA测序相结合。使用计算建模，PIC-seq系统地映射原位细胞相互作用并表征其分子串扰。我们应用PIC-seq来询问不同的相互作用，包括新生小鼠肺中的免疫上皮PIC。针对T细胞与树突状细胞（DCs）在体内外的相互作用，我们绘制了T细胞与DCs相互作用的偏好图，发现调节性T细胞是小鼠引流淋巴结中与DCs相互作用的主要T细胞亚型。对T细胞-DC对的分析揭示了病原体呈递的迁移性DC和T细胞之间的相互作用特异性程序。PIC-seq提供了一种直接和广泛适用的技术，以高分辨率表征细胞间相互作用特异性途径。
PIC-seq characterizes cellular crosstalk by sorting and sequencing physically interacting cells.Crosstalk between neighboring cells underlies many biological processes, including cell signaling, proliferation and differentiation. Current single-cell genomic technologies profile each cell separately after tissue dissociation, losing information on cell-cell interactions. In the present study, we present an approach for sequencing physically interacting cells (PIC-seq), which combines cell sorting of physically interacting cells (PICs) with single-cell RNA-sequencing. Using computational modeling, PIC-seq systematically maps in situ cellular interactions and characterizes their molecular crosstalk. We apply PIC-seq to interrogate diverse interactions including immune-epithelial PICs in neonatal murine lungs. Focusing on interactions between T cells and dendritic cells (DCs) in vitro and in vivo, we map T cell-DC interaction preferences, and discover regulatory T cells as a major T cell subtype interacting with DCs in mouse draining lymph nodes. Analysis of T cell-DC pairs reveals an interaction-specific program between pathogen-presenting migratory DCs and T cells. PIC-seq provides a direct and broadly applicable technology to characterize intercellular interaction-specific pathways at high resolution.