The study investigates colonic epithelial differentiation mechanisms crucial for understanding inflammatory conditions and cancer. Using colon organoids from healthy tissue of colorectal cancer patients, researchers induced differentiation towards enterocytes and goblet cells, the major colonic epithelial lineages. They found that activating the BMP pathway favored enterocyte differentiation, while inhibiting the Notch pathway promoted goblet cell differentiation. Combining BMP pathway activation with Notch inhibition led to balanced induction of both lineages. However, colon tumor organoids showed poor response to differentiation stimuli. Additionally, the effects of calcitriol on differentiation were explored, showing its ability to modulate BMP and Notch signaling, favoring stemness features in normal organoids.