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

• Published in: Science (American Association for the Advancement of Science) Vol. 385; no. 6709; p. eadp2065
• Main Authors: Gao, Xin, Carpenter, Randall S, Boulais, Philip E, Zhang, Dachuan, Marlein, Christopher R, Li, Huihui, Smith, Matthew, Chung, David J, Maryanovich, Maria, Will, Britta, Steidl, Ulrich, Frenette, Paul S
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 09.08.2024
• Subjects: Adult Stem Cells - physiology; Animal models; Animals; Antigens, Differentiation; Blood circulation; Bone growth; Bone marrow; c-Kit protein; Cell culture; Cell membranes; Cell surface; Chemokine receptors; Colony-stimulating factor; CXCR4 protein; Granulocyte colony-stimulating factor; Growth factors; Hematopoietic Stem Cell Mobilization - methods; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Hematopoietic system; Homeostasis; Humans; Kinases; Leukocytes (granulocytic); Macrophages; Macrophages - metabolism; Membranes; Mice; Mice, Inbred C57BL; Microenvironments; Molecular modelling; Numbers; Peripheral blood; Pharmacology; Plasma membranes; Protein-tyrosine kinase receptors; Proteins; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Repopulation; Retention; Sialic Acid Binding Ig-like Lectin 1 - metabolism; Stem cell factor; Stem Cell Niche; Stem cell transplantation; Stem cells; Trogocytosis; Tyrosine
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.adp2065

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.