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 precise mechanisms by which individual stem cells exit the marrow are not understood. This study identified cell-extrinsic and molecular determinants...

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Vydáno v:Science (American Association for the Advancement of Science) Ročník 385; číslo 6709; s. eadp2065
Hlavní autoři: 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
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 09.08.2024
Témata:
Adult Stem Cells - physiology
Animals
Antigens, Differentiation
Hematopoietic Stem Cell Mobilization - methods
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - physiology
Humans
Macrophages - metabolism
Mice
Mice, Inbred C57BL
Proto-Oncogene Proteins c-kit - genetics
Proto-Oncogene Proteins c-kit - metabolism
Sialic Acid Binding Ig-like Lectin 1 - metabolism
Stem Cell Niche
Trogocytosis
ISSN:1095-9203, 1095-9203
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Popis
Shrnutí: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.
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.adp2065