The multicellular coordination that underlies tissue homeostasis and disease progression is of fundamental interest^1,2,3,4,5. However, how diverse cell types are organized within tissue niches for cohesive functioning remains largely unknown. Here we systematically characterized cross-tissue coordinated cellular modules in healthy tissues, uncovering their spatiotemporal dynamics and phenotypic associations, and examined their rewiring in cancer. We first compiled a comprehensive single-cell transcriptomic atlas from 35 human tissues, revealing substantial inter-tissue variability in cellular composition. By leveraging covariance in cellular abundance, we identified 12 cellular modules with distinct cellular compositions, tissue prevalences and spatial organizations, and demonstrated coordinated intercellular communication within cellular modules using in situ spatial and in vivo perturbation data. Among them, two immune cellular modules in the spleen showed contrasting chronological dynamics with ageing. Analysis of multicellular changes in the breast revealed a menopausal trajectory associated with fibroblast dynamics. Furthermore, interrogation across cancer types uncovered simultaneous rewiring of two types of multicellular ecosystem during tumour progression, including the loss of tissue-specific healthy organization and the emergence of a convergent cancerous ecosystem. These findings reveal fundamental organizing principles of multicellular ecosystems in health and cancer, laying a foundation for further investigations into tissue-level functional coordination across diverse contexts.

组织稳态和疾病进展的基础多细胞协调具有根本意义 ^1,2,3,4,5。然而，不同的细胞类型如何在组织生态位中组织以实现内聚功能在很大程度上仍然未知。在这里，我们系统地表征了健康组织中跨组织协调的细胞模块，揭示了它们的时空动力学和表型关联，并检查了它们在癌症中的重新布线。我们首先从 35 个人体组织中汇编了一份全面的单细胞转录组图谱，揭示了细胞组成的巨大组织间差异。通过利用细胞丰度的协方差，我们确定了 12 个具有不同细胞组成、组织流行率和空间组织的细胞模块，并使用原位空间和体内扰动数据证明了细胞模块内的协调细胞间通讯。其中，脾脏中的两个免疫细胞模块表现出与衰老形成鲜明对比的时间动力学。对乳房多细胞变化的分析揭示了与成纤维细胞动力学相关的更年期轨迹。此外，跨癌症类型的询问揭示了肿瘤进展过程中两种类型的多细胞生态系统同时重新布线，包括组织特异性健康组织的丧失和趋同癌性生态系统的出现。这些发现揭示了健康和癌症中多细胞生态系统的基本组织原理，为进一步研究不同背景下的组织水平功能协调奠定了基础。