Extended Data Fig. 7: Schematic illustration of the mechanism by which loss of Clu function attenuates myeloid-biased differentiation in aged HSCs.
From: Clusterin drives myeloid bias in aged hematopoietic stem cells by regulating mitochondrial function
Age-dependent increase in Clu expression leads to an increase in mitochondrial fusion through interaction with Mfn2. This in turn facilitates excessive mitochondrial OXPHOS with ROS, which activates the p38 MAPK signaling pathway resulting in increased Cebpb expression. As a key transcription factor driving myeloid cell differentiation, upregulation of Cebpb leads to myeloid-biased differentiation in aged HSCs. Depletion of Clu can reduce the biased differentiation and alleviate age-associated functional decline through reducing mitochondrial hyperfusion, improving mitophagy and restoring youthful metabolism. Illustration created with BioRender.com.
