Rapid Activation of Hematopoietic Stem Cells

Abstract

Adult Hematopoietic Stem Cells (HSCs) in the bone marrow (BM) are quiescent. Following perturbations, such as blood loss or infection, HSCs may undergo activation to accelerate the production of needed effector blood and immune cells. Surprisingly, little is known about the earliest stages of HSC activation. We utilize surface markers of HSC activation, CD69, and CD317, revealing response as early as 2 h after stimulation. 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 and progenitors in the BM. Finally, we find a positive correlation between the expression of surface activation markers and early exit from quiescence into proliferation. Our data show that the premier response of adult stem cells to immune stimulation is rapid, sensitive, and directly leads to proliferation.