Reactive oxygen species in hematopoietic stem cells affect culture outcomes under inflammatory conditions

Abstract

Functions of hematopoietic stem cells (HSCs) are tightly regulated to ensure lifelong normal hematopoiesis within the bone marrow (BM) niche. While HSCs’ status is well orchestrated to uphold their stemness, the fate of HSCs can be altered in response to inflammatory signals caused by environmental changes. The influence on HSCs of inflammatory changes within BM has been explored; however, how each inflammatory cytokine affects the maintenance or differentiation of HSCs remains to be fully elucidated. Considering recent studies demonstrating that reactive oxygen species (ROS) influence HSCs’ fates, we conducted a comprehensive analysis of the effects of seven major inflammatory cytokines on proliferation, differentiation, and ROS level regulation in HSCs / hematopoietic stem/progenitor cells (HSPCs). Our study indicates that inflammatory cytokines in general push HSCs/HSPCs into differentiation, but vary significantly with respect to retention of primitive cells. With definition by cellular immunophenotypes, TNF-α, IFN-γ, and type I IFNs stimulated loss of HSCs, whereas TGF-β and IL-6, and possibly IL1β as well, showed potential to retain them. Of note is that unaltered ROS levels were compatible with HSC retention, while drastic change, either increase or decrease, in ROS levels presaged HSC loss. Detailed evaluation of links between inflammatory cytokines and ROS regulation appears likely to prove important in understanding HSC biology and translating basic science into clinical applications.