FOXO activity adaptation safeguards the hematopoietic stem cell compartment in hyperglycemia.

ABSTRACT: Hematopoietic stem cell (HSC) activity is tightly controlled to ensure the integrity of the hematopoietic system during the organism's lifetime. How the HSC compartment maintains its long-term fitness in conditions of chronic stresses associated with systemic metabolic disorders is poorly understood. In this study, we show that obesity functionally affects the long-term function of the most immature engrafting HSC subpopulation. We link this altered regenerative activity to the oxidative stress and the aberrant constitutive activation of the AKT signaling pathway that characterized the obese environment. In contrast, we found minor disruptions of the HSC function in obese mice at steady state, suggesting that active mechanisms could protect the HSC compartment from its disturbed environmen

SUBMITTER: Govindarajah V 

PROVIDER: S-EPMC7656925 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature