A cell’s function is influenced by the environment, or niche, in which it resides. Studies of niches usually require assumptions about the cell types present, which impedes the discovery of new cell types or interactions. Here we describe ProximID, an approach for building a cellular network based on physical cell interaction and single-cell mRNA sequencing, and show that it can be used to discover new preferential cellular interactions without prior knowledge of component cell types. ProximID found specific interactions between megakaryocytes and mature neutrophils and between plasma cells and myeloblasts and/or promyelocytes (precursors of neutrophils) in mouse bone marrow, and it identified a Tac1⁺ enteroendocrine cell–Lgr5⁺ stem cell interaction in small intestine crypts. This strategy can be used to discover new niches or preferential interactions in a variety of organs.

细胞的功能受其所处环境或环境的影响。生态位的研究通常需要对存在的细胞类型进行假设，这阻碍了新细胞类型或相互作用的发现。在这里，我们介绍ProximID，这是一种基于物理细胞相互作用和单细胞mRNA测序构建细胞网络的方法，并表明它可以用于发现新的优先细胞相互作用，而无需事先了解组成细胞类型。ProximID在小鼠骨髓中发现了巨核细胞与成熟嗜中性粒细胞之间以及浆细胞与成肌细胞和/或早幼粒细胞（嗜中性粒细胞的前体）之间的特异性相互作用，并鉴定出Tac1 ⁺肠内分泌细胞Lgr5 ⁺小肠隐窝中的干细胞相互作用。此策略可用于发现各种器官中的新壁ni或优先相互作用。