Distinct roles for NF-κB in hematopoietic stem cells and the bone marrow milieu in promoting hematopoietic aging

proinflammatory bone marrow milieu, as observed functionally, epigenomically, and transcriptomically. A single-cell RNA sequencing (scRNA-seq) HSPC labeling framework enables comparisons with aged murine and human HSC datasets, documenting an association between HSC-intrinsic NF-κB activity and quiescence but not myeloid bias. These findings delineate separate regulatory mechanisms that underlie the three hallmarks of hematopoietic aging, suggesting that they are specifically and independently therapeutically targetable.