Environmental Enrichment Induces Pericyte and IgA-Dependent Wound Repair and Lifespan Extension in a Colon Tumor Model (RNAseq). Mus musculus

Environmental enrichment (EE) replicates mind-body therapy by providing complex housing to laboratory animals to improve their activity levels, behavior and social interactions. Using a Tcf4Het/+ ApcMin/+-mediated model of colon tumorigenesis, we found that EE vastly improved the survival of tumor-bearing animals, with differential effect on tumor load in male compared to female animals. Analysis of Tcf4Het/+ ApcMin/+ males showed drastically reduced expression of circulating inflammatory cytokines and induced nuclear hormone receptor signaling, both of which are common in the wound repair process. Interestingly, EE provoked tumor wound repair resolution through revascularization, plasma cell recruitment and IgA secretion, replacement of glandular tumor structures with pericytes in a process reminiscent of scarring, and normalization of microbiota. These EE-dependent changes likely underlie the profound improvement in survival of colon-tumor-bearing Tcf4Het/+ ApcMin/+ males. Our studies highlight the exciting promise of EE in the design of future therapeutic strategies for colon cancer patients. Overall design: Four samples from EE and NE (non-enriched controls) were analyzed

环境丰富化（Environmental enrichment，EE）通过为实验动物提供复杂饲养环境，模拟心身疗法，以改善其活动水平、行为表现与社交互动能力。本研究采用Tcf4Het/+ ApcMin/+介导的结肠肿瘤发生模型，发现EE可显著提升荷瘤动物的生存率，且对雌雄荷瘤个体的肿瘤负荷产生了差异化影响。对Tcf4Het/+ ApcMin/+雄性小鼠的分析显示，其循环炎性细胞因子的表达水平大幅下调，同时核激素受体信号通路被激活——这两类变化均常见于伤口修复进程中。有趣的是，EE通过血管新生、浆细胞募集与免疫球蛋白A（IgA）分泌，促进了肿瘤相关伤口修复的消退；其还以类似瘢痕形成的过程，用周细胞替换腺体样肿瘤结构，并实现了微生物群的稳态恢复。这些依赖于EE的变化，大概率是携带结肠肿瘤的Tcf4Het/+ ApcMin/+雄性小鼠生存率显著改善的核心机制。本研究凸显了EE在未来结肠癌治疗策略开发中的广阔应用前景。整体实验设计：本研究共分析了来自环境丰富化组（EE）与非富集饲养对照组（non-enriched controls，NE）的4份样本。