Mammalian cells display a broad spectrum of phenotypes, morphologies, and functional niches within biological systems. Our understanding of mechanisms at the individual cellular level, and how cells function in concert to form tissues, organs and systems, has been greatly facilitated by centuries of extensive work to classify and characterize cell types. Classic histological approaches are now complemented with advanced single-cell sequencing and spatial transcriptomics for cell identity studies. Emerging data suggests that additional levels of information should be considered, including the subcellular spatial distribution of molecules such as RNA and protein, when classifying cells. In this Perspective piece we describe the importance of integrating cell transcriptional state with tissue and subcellular spatial and temporal information for thorough characterization of cell type and state. We refer to recent studies making use of single cell RNA-seq and/or image-based cell characterization, which highlight a need for such in-depth characterization of cell populations. We also describe the advances required in experimental, imaging and analytical methods to address these questions. This Perspective concludes by framing this argument in the context of projects such as the Human Cell Atlas, and related fields of cancer research and developmental biology.

哺乳动物细胞在生物系统中表现出广泛的表型、形态和功能生态位。几个世纪以来对细胞类型进行分类和表征的广泛工作极大地促进了我们对个体细胞水平的机制以及细胞如何协同作用形成组织、器官和系统的理解。经典的组织学方法现在得到了先进的单细胞测序和空间转录组学的补充，用于细胞身份研究。新出现的数据表明，在对细胞进行分类时，应考虑额外级别的信息，包括 RNA 和蛋白质等分子的亚细胞空间分布。在这篇透视文章中，我们描述了将细胞转录状态与组织和亚细胞空间和时间信息整合以全面表征细胞类型和状态的重要性。我们参考了最近利用单细胞 RNA 测序和/或基于图像的细胞表征的研究，这些研究强调了对细胞群进行如此深入的表征的必要性。我们还描述了解决这些问题所需的实验、成像和分析方法的进步。本观点的结论是在人类细胞图谱等项目以及癌症研究和发育生物学的相关领域的背景下构建这一论点。