颜林林 (2022-08-05 21:59):
#paper doi:10.1038/s41586-022-05028-x Nature, 2022, A physical wiring diagram for the human immune system. 本文开发了一种名为SAVEXIS(scalable arrayed multi-valent extracellular interaction screen)的方法,高通量地筛选存在相互作用关系的细胞表面蛋白对,并用多种实验方法、文献支持、单细胞数据等来对所发现的结果进行验证,得到一套高质量的免疫细胞相互作用的连接关系图谱。
IF:50.500Q1 Nature, 2022-08. DOI: 10.1038/s41586-022-05028-x PMID: 35922511
A physical wiring diagram for the human immune system
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Abstract:
The human immune system is composed of a distributed network of cells circulating throughout the body, which must dynamically form physical associations and communicate using interactions between their cell-surface proteomes. Despite their therapeutic potential, our map of these surface interactions remains incomplete. Here, using a high-throughput surface receptor screening method, we systematically mapped the direct protein interactions across a recombinant library that encompasses most of the surface proteins that are detectable on human leukocytes. We independently validated and determined the biophysical parameters of each novel interaction, resulting in a high-confidence and quantitative view of the receptor wiring that connects human immune cells. By integrating our interactome with expression data, we identified trends in the dynamics of immune interactions and constructed a reductionist mathematical model that predicts cellular connectivity from basic principles. We also developed an interactive multi-tissue single-cell atlas that infers immune interactions throughout the body, revealing potential functional contexts for new interactions and hubs in multicellular networks. Finally, we combined targeted protein stimulation of human leukocytes with multiplex high-content microscopy to link our receptor interactions to functional roles, in terms of both modulating immune responses and maintaining normal patterns of intercellular associations. Together, our work provides a systematic perspective on the intercellular wiring of the human immune system that extends from systems-level principles of immune cell connectivity down to mechanistic characterization of individual receptors, which could offer opportunities for therapeutic intervention.
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