Tissue and cellular spatiotemporal dynamics in colon aging [scRNA-seq]

Tissue structure and molecular circuitry in the colon can be profoundly impacted by systemic age-related effects, but many of the underlying molecular cues remain unclear. Here, we built a cellular and spatial atlas of the colon across three anatomical regions and 11 age groups, encompassing ~1,500 mouse gut tissues profiled by spatial transcriptomics and ~400,000 single nucleus RNA-seq profiles. We developed a new computational framework, cSplotch, which learns a hierarchical Bayesian model of spatially resolved cellular expression associated with age, tissue region, and sex, by leveraging histological features to share information across tissue samples and data modalities. Using this model, we identified cellular and molecular gradients along the adult colonic tract and across the main crypt axis, and multicellular programs associated with aging in the large intestine. Our multi-modal framework for the investigation of cell and tissue organization can aid in the understanding of cellular roles in tissue-level pathology. snRNA-seq profiling of colon tissue from C57BL/6J mice ranging in age from 0d to 2yr结肠的组织结构与分子调控环路可受到系统性衰老相关效应的显著影响，但其背后的诸多核心分子线索仍未明确。本研究构建了覆盖三个解剖区域与11个年龄组的结肠细胞与空间图谱，共包含约1500份经空间转录组（spatial transcriptomics）测序分析的小鼠肠道组织样本，以及约40万个单细胞核RNA测序（single nucleus RNA-seq）谱数据。我们开发了一款全新的计算框架cSplotch，该框架通过利用组织学特征在不同组织样本与数据模态间共享信息，构建了与年龄、组织区域及性别相关的空间分辨细胞表达分层贝叶斯模型。借助该模型，我们鉴定出成年结肠通路沿轴向以及主要隐窝轴的细胞与分子梯度特征，同时发现了大肠衰老相关的多细胞程序。本研究用于探究细胞与组织架构的多模态框架，可助力解析细胞在组织层面病理过程中的功能角色。本数据集涵盖了0日龄至2年龄C57BL/6J小鼠结肠组织的单细胞核RNA测序谱数据。