Metabolic regulation of intestinal stem cell fate

Metabolism is a multifaceted network of chemical, enzyme catalyzed reactions in between in- and outflow of cellular matter. By providing energy, cellular building blocks and detoxifying harmful substances it is the core machinery maintaining the existence and propagation of all life forms. Historically, metabolism has been seen as a passive executioner of cell signaling. Previously we showed that a glucose metabolizing Hexosamine Biosynthesis Pathway (HBP) plays an important role in adjusting stem cell proliferation in accordance with the prevailing nutritional condition through insulin mediated satiety signal (Mattila et al. 2018). Hence, hexosamine synthesis defines the stem cell responsiveness to systemic or niche-derived growth signals. Uncovering specific molecular mechanisms coupling metabolic pathway activities, such as the HBP, and traditional cellular signaling pathways, may offer novel means to increase the efficacy of future stem cell therapies.

Hexosamine synthesis pathway scheme

Schematics of the hexosamine biosynthesis pathway (HBP). HBP is a nutrient-responsive metabolic pathway, incorporating intracellular glucose, glutamine, acetyl-CoA, and UTP into the synthesis of UDP-GlcNAc, a substrate for macromolecule glycosylation.