Aging and leukemic evolution of hematopoietic stem cells under various stress conditions

摘要

Factors that promote HSC aging and rejuvenation strategies for aged HSCs. N-acetyl cysteine (NAC) and p38 mitogen-activated protein kinase (MAPK) inhibitor rejuvenate aged hematopoietic stem cells (HSCs) by reducing reactive oxygen species (ROS) levels. Cdc42 activity inhibitor (CASIN) increases the percentage of polarized cells, restores the spatial distribution of H4 at lysine 16 acetylation, increases lymphoid output, and reduces myeloid lineage output. Sirt3 overexpression restores the long-term competitive repopulation ability. Sirt7 overexpression rescues myeloid-biased differentiation. ABT263 (navitoclax), a BCL-2- and BCL-xL-specific inhibitor, selectively kills senescent cells. Supplementation of a sympathomimetic acting selectively on adrenoreceptor β3 rejuvenates the function of aged HSCs. The red and blue arrows indicate aging and rejuvenation, respectively