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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| Veröffentlicht in: | Science (American Association for the Advancement of Science) Jg. 385; H. 6709; S. eadp2065 |
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| Format: | Journal Article |
| Sprache: | Englisch |
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United States
09.08.2024
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| ISSN: | 1095-9203, 1095-9203 |
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| Abstract | 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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| AbstractList | 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.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. 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. |
| Author | Gao, Xin Smith, Matthew Frenette, Paul S Carpenter, Randall S Boulais, Philip E Will, Britta Li, Huihui Maryanovich, Maria Steidl, Ulrich Zhang, Dachuan Marlein, Christopher R Chung, David J |
| Author_xml | – sequence: 1 givenname: Xin orcidid: 0000-0001-8520-5109 surname: Gao fullname: Gao, Xin organization: Wisconsin Blood Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA – sequence: 2 givenname: Randall S orcidid: 0000-0002-0613-6094 surname: Carpenter fullname: Carpenter, Randall S organization: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA – sequence: 3 givenname: Philip E surname: Boulais fullname: Boulais, Philip E organization: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA – sequence: 4 givenname: Dachuan orcidid: 0000-0002-1746-275X surname: Zhang fullname: Zhang, Dachuan organization: Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 5 givenname: Christopher R surname: Marlein fullname: Marlein, Christopher R organization: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA – sequence: 6 givenname: Huihui orcidid: 0000-0003-4335-6050 surname: Li fullname: Li, Huihui organization: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA – sequence: 7 givenname: Matthew orcidid: 0000-0001-9365-8933 surname: Smith fullname: Smith, Matthew organization: Wisconsin Blood Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA – sequence: 8 givenname: David J orcidid: 0000-0003-0469-839X surname: Chung fullname: Chung, David J organization: Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 9 givenname: Maria orcidid: 0000-0002-2015-0538 surname: Maryanovich fullname: Maryanovich, Maria organization: Montefiore-Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine-Montefiore Health System, Bronx, NY, USA – sequence: 10 givenname: Britta orcidid: 0000-0002-9534-6690 surname: Will fullname: Will, Britta organization: Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY, USA – sequence: 11 givenname: Ulrich orcidid: 0000-0002-9458-1795 surname: Steidl fullname: Steidl, Ulrich organization: Department of Oncology, Albert Einstein College of Medicine, Bronx, NY, USA – sequence: 12 givenname: Paul S surname: Frenette fullname: Frenette, Paul S organization: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA |
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| Snippet | Hematopoietic stem cells (HSCs) are routinely mobilized from the bone marrow (BM) to the blood circulation for clinical transplantation. However, the precise... |
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| SubjectTerms | 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 |
| Title | Regulation of the hematopoietic stem cell pool by C-Kit-associated trogocytosis |
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