Miyeko Mana

Keywords single-cell genomics liver metabolism chronic stress response tissue memory epigenetic priming genetic perturbation computational methods development Introduction During chronic stress, cells must buffer environmental perturbations to ensure their own survival while contributing to tissue functions necessary for organismal health.1 Hepatocytes perform wide-ranging functions, including nutrient metabolism, protein secretion, and chemical detoxification.2,3 Moreover, they possess...

Highlights • HFD augments intestinal stemness through PPARδ and PPARα • A PPAR-FAO program enhances stemness and tumorigenicity in a HFD • Loss or inhibition of Cpt1a-mediated FAO blunts the HFD-enhancing effects in ISCs • Early intestinal tumors arising from HFD ISCs are highly sensitive to FAO inhibition Summary Obesity is an established risk factor for cancer in many tissues.

Abstract A decline in stem cell function impairs tissue regeneration during ageing, but the role of the stem-cell-supporting niche in ageing is not well understood. The small intestine is maintained by actively cycling intestinal stem cells that are regulated by the Paneth cell niche1,2. Here we show that the regenerative potential of human and mouse intestinal epithelium diminishes with age owing to defects in both stem cells and their niche.