The Role of Ceramides in the Intestinal Stem Cell

SUMMARY Exposing cells to excessive amounts of lipid and other nutrients promotes the accumulation of sphingolipids such as ceramides, which alter tissue metabolism to help cells adapt to the abundance of excessive, detergent-like fatty acids (Chaurasia et al., Science, 2019). Studies described herein reveal that ceramides play particularly prominent roles in the gastrointestinal tract, where they increase fatty acid uptake into intestinal stem cells to promote regeneration of the intestinal epithelium. Using organoid, fly, and mouse models, we will dissect the mechanisms linking these sphingolipids to the control of intestinal stem cell metabolism, proliferation, and differentiation. Moreover, we will explore the contribution of sphingolipids as signals of lipid excess that drive gastrointestinal tumorigenesis and invasiveness. Findings obtained from these studies could uncover new nutrient-sensing machinery that modulates intestinal stem cell proliferation and leads to new pharmacological approaches for manipulating sphingolipids to improve gut health.