Age-related dysregulation of intestinal epithelium fucosylation is linked to an increased risk of colon cancer.

Colon cancer affects people of all ages. However, its frequency, as well as the related morbidity and mortality, are high among older adults. The complex physiological changes in the aging gut substantially limit the development of cancer therapies. Here, we identify a potentially unique intestinal microenvironment that is linked with an increased risk of colon cancer in older adults. Our findings show that aging markedly influenced persistent fucosylation of the apical surfaces of intestinal epithelial cells, which resulted in a favorable environment for tumor growth. Furthermore, our findings shed light on the importance of the host-commensal interaction, which facilitates the dysregulation of fucosylation and promotes tumor growth as people get older. We analyzed colonic microbial populations at the species level to find changes associated with aging that could contribute to the development of colon cancer. Analysis of single-cell RNA-sequencing data from previous publications identified distinct epithelial cell subtypes involved in dysregulated fucosylation in older adults. Overall, our study provides compelling evidence that excessive fucosylation is associated with the development of colon cancer, that age-related changes increase vulnerability to colon cancer, and that a dysbiosis in microbial diversity and metabolic changes in the homeostasis of older mice dysregulate fucosylation levels with age.

Arsenite Exposure to Human RPCs (HRTPT) Produces a Reversible Epithelial Mesenchymal Transition (EMT): In-Vitro and In-Silico Study.

The human kidney is known to possess renal progenitor cells (RPCs) that can assist in the repair of acute tubular injury. The RPCs are sparsely located as single cells throughout the kidney. We recently generated an immortalized human renal progenitor cell line (HRTPT) that co-expresses PROM1/CD24 and expresses features expected on RPCs. This included the ability to form nephrospheres, differentiate on the surface of Matrigel, and undergo adipogenic, neurogenic, and osteogenic differentiation. These cells were used in the present study to determine how the cells would respond when exposed to nephrotoxin. Inorganic arsenite (iAs) was chosen as the nephrotoxin since the kidney is susceptible to this toxin and there is evidence of its involvement in renal disease. Gene expression profiles when the cells were exposed to iAs for 3, 8, and 10 passages (subcultured at 1:3 ratio) identified a shift from the control unexposed cells. The cells exposed to iAs for eight passages were then referred with growth media containing no iAs and within two passages the cells returned to an epithelial morphology with strong agreement in differential gene expression between control and cells recovered from iAs exposure. Results show within three serial passages of the cells exposed to iAs there was a shift in morphology from an epithelial to a mesenchymal phenotype. EMT was suggested based on an increase in known mesenchymal markers. We found RPCs can undergo EMT when exposed to a nephrotoxin and undergo MET when the agent is removed from the growth media.