Study to be published in Cell shows that when there is an infection, HSCs develop into immune system cells in the organ where they reside.

Harvard Medical School investigators found that upon encountering an invader, hematopoietic stem cells (HSC) can divide and mature into immune system cells on the spot.

Scientists have known that a fraction of HSCs will sometimes migrate from the bone marrow into the bloodstream. To understand why, they began by extracting lymph samples from the thoracic duct of a mouse, which routes the body’s excess fluids into circulation.

After screening, they discovered an extremely small population of blood stem cells. Further tests, which involved mice genetically engineered so that their blood stem cells could be detected through fluorescent microscopy, revealed that these cells were also scattered throughout visceral organs such as lthe iver, heart, and lungs.

“Taken all together, a picture developed suggesting that these cells migrated from the marrow and into the circulation where they would then leak out and enter the tissue,” says team leader, Steffen Massberg, M.D., a postdoctoral researcher and cardiologist. “After that, the thoracic duct would empty them back into the circulation, where they could re-enter the marrow.

“But the question was, why,” notes Dr. Massberg. “What exactly are they doing?” To figure this out, the researchers injected a bacterial endotoxin into the mouse tissue.

They found that after residing for a while in the organ tissue, the stem cells receive a lipid signal that enables them to exit into the thoracic duct. When the receptors on the stem-cell surface that detect pathogens become active, the cell’s ability to receive the lipid signal is blocked. The stem cells literally get stuck in the tissue, where they are then triggered to proliferate into immune cells, the scientists explain.

The paper will be published in the November 30 edition of Cell.

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