Diet-omics in the Study of Urban and Rural Crohn disease Evolution (SOURCE) cohort.

Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirror those seen in CD. Ileal transcriptomics highlights personal metabolic and immune gene expression modules, that are directly linked to potential protective dietary exposures (coffee, manganese, vitamin D), fecal metabolites, and the microbiome. Bacteria-associated metabolites are primarily linked with host immune modules, whereas diet-linked metabolites are associated with host epithelial metabolic functions.

Evolution of fibroblasts in the lung metastatic microenvironment is driven by stage-specific transcriptional plasticity.

Mortality from breast cancer is almost exclusively a result of tumor metastasis, and lungs are one of the main metastatic sites. Cancer-associated fibroblasts are prominent players in the microenvironment of breast cancer. However, their role in the metastatic niche is largely unknown. In this study, we profiled the transcriptional co-evolution of lung fibroblasts isolated from transgenic mice at defined stage-specific time points of metastases formation. Employing multiple knowledge-based platforms of data analysis provided powerful insights on functional and temporal regulation of the transcriptome of fibroblasts. We demonstrate that fibroblasts in lung metastases are transcriptionally dynamic and plastic, and reveal stage-specific gene signatures that imply functional tasks, including extracellular matrix remodeling, stress response, and shaping the inflammatory microenvironment. Furthermore, we identified Myc as a central regulator of fibroblast rewiring and found that stromal upregulation of Myc transcriptional networks is associated with disease progression in human breast cancer.