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

• 成果类型: Article
• 署名作者: 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.
• 署名单位: Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; University of Wisconsin System; University of Wisconsin Madison; Shanghai Jiao Tong University; Memorial Sloan Kettering Cancer Center; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11418
• DOI: 10.1126/science.adp2065
• 发表日期: 2024-08-09
• 关键词: factor receptor/c-kit; progenitor cells; dendritic cells; macrophages; mobilization; erythropoiesis; homeostasis; inhibition; depletion; proteins

摘要

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.