Immune Excitation of Hematopoietic Stem Cells

Hematopoietic Stem Cells (HSCs) are the source of blood and immune cells thanks to their long-term self-renewal and multipotency. During everyday healthy life, HSCs are mostly quiescent in the bone marrow. Following infection or inflammation HSCs might gain activation, presumably accelerating the generation of the needed blood and immune cells. Surprisingly, however, our knowledge regarding various pathogens' ability to perturb HSCs is minimal. Better models and markers are needed.
Better identification of HSCs during infection allowed us to reveal molecular insights and the expression of surface activation markers. HSC's activation follows many, but not all, types of immune stimuli. Our current study further reveals that HSC's activation is faster and broader than previously thought, as evident for Stem- and progenitors as early as 2 hours. The response is systemic, very sensitive, and dose-response down to surprisingly low amounts of stimulation. Recent studies challenge the concepts of HSCs' contribution to emergency hematopoiesis.
Chronic activation may cause depleted HSCs' potency and increase the risk of malignancies. We find extraordinary impact following prolonged bacterial infection in mice and aim to study the recovery phase. In parallel, using the pre-disposed p53-mutant model, we reveal that chronic immune stimulation might cause T-cell lymphoma.
Changing concepts of hematopoiesis highlight interest in dynamic studies of HSCs. New data will allow for preserving the potency for a longer and healthier life.