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Hes1 Loss leads to HSC Exhaustion

A recent STEM CELLS study from the lab of Wei Du (West Virginia University, USA) established that Hes1‐deficient hematopoietic stem cells (HSCs) undergo exhaustion under replicative stress. Ma et al. discovered that the deletion of Hes1 alters HSC function through the deregulation of genes related to PPARγ signaling and fatty acid oxidation (FAO), leading to augmented FAO; however, PPARγ targeting or FAO inhibition ameliorated the repopulating defects of Hes1‐deficient HSCs by improving quiescence. Together, these findings identify a novel role of Hes1 in regulating stress hematopoiesis and provide mechanistic insight into the function of Hes1 in HSC maintenance.