Regulation of the hematopoietic stem cell pool by c-Kit-associated trogocytosis

Hematopoietic stem cells (HSCs) are routinely mobilized from the bone marrow (BM) to the blood circulation for clinical transplantation. However, the mechanisms by which HSCs exit the marrow are not well understood. We found that most BM HSCs present the macrophage marker F4/80 on their cell surface. Upon enforced mobilization induced by granulocyte-colony-stimulating factor or CXCR4 antagonist, F4/80+ HSCs were selectively retained in the BM while F4/80— HSCs were mobilized to the blood. Remarkably, F4/80 was acquired through direct transfer via c-Kit-mediated trogocytosis from BM resident macrophages in mouse and human settings. Our study uncovers a function for BM-resident macrophages in controlling the HSC mobilizable pool, and identifies mechanisms that may be used to improve HSC yield for transplantation. mRNA profiles of sorted F4/80 negative and F4/80 positive hematopoietic stem cells from bone marrow in triplicates