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

• DOI: 10.1126/science.adp2065
• Publication Date: 2024-08-08T18:06:46Z
• Authors: Xin Gao; Randall S. Carpenter; Philip E. Boulais; Dachuan Zhang; Christopher R. Ma...; Huihui Li; Matthew Smith; David J. Chung; Maria Maryanovich; Britta Will; Ulrich Steidl; Paul S. Frenette
• Keywords: 0303 health sciences; Sialic Acid Binding Ig-like Lectin 1; Macrophages; Hematopoietic Stem Cells; Trogocytosis; Antigens, Differentiation; Hematopoietic Stem Cell Mobilization; Mice, Inbred C57BL; Mice; Adult Stem Cells; Proto-Oncogene Proteins c-kit; 03 medical and health sciences; Animals; Humans; Stem Cell Niche

Hematopoietic stem cells (HSCs) are routinely mobilized from the bone marrow (BM) to the blood circulation for clinical transplantation. However, the precise mechanisms by which individual stem cells exit the marrow are not understood. This study identified cell-extrinsic and molecular determinants of a mobilizable pool of blood-forming stem cells. We found that a subset of HSCs displays macrophage-associated markers on their cell surface. Although fully functional, these HSCs are selectively niche-retained as opposed to stem cells lacking macrophage markers, which exit the BM upon forced mobilization. Macrophage markers on HSCs could be acquired through direct transfer by trogocytosis, regulated by receptor tyrosine-protein kinase C-Kit (CD117), from BM-resident macrophages in mouse and human settings. Our study provides proof of concept that adult stem cells utilize trogocytosis to rapidly establish and activate function-modulating molecular mechanisms.