Rapid Activation of Hematopoietic Stem Cells

Abstract

Adult Hematopoietic Stem Cells (HSCs) are quiescent in the bone marrow (BM). Following perturbations, such as blood loss or infection, HSCs may activate to accelerate the production of needed effector blood and immune cells. Surprisingly little is known about the earliest stages of HSCs activation. We utilize surface markers of HSC activation, CD69 and CD317, revealing very early response in as little as 2 h. The dynamic expression of HSC activation markers varies between viral-like (poly-Inosinic-poly-Cytidylic) or bacterial-like (Lipopolysaccharide) immune stimuli. We further quantify the dose-response, demonstrating a low-threshold and similar sensitivity of HSCs like other progenitors in the BM. Finally, we find a positive correlation between surface activation markers expression and the early exit from quiescence into proliferation following immune stimulation. Our data show that premier response of adult stem cells to immune stimulation is rapid, sensitive, and directly leading towards proliferation.