دورية أكاديمية
SDF-1 dynamically mediates megakaryocyte niche occupancy and thrombopoiesis at steady state and following radiation injury.
| العنوان: | SDF-1 dynamically mediates megakaryocyte niche occupancy and thrombopoiesis at steady state and following radiation injury. |
|---|---|
| المؤلفون: | Niswander LM; Center for Pediatric Biomedical Research, Department of Pediatrics, and Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY., Fegan KH; Center for Pediatric Biomedical Research, Department of Pediatrics, and., Kingsley PD; Center for Pediatric Biomedical Research, Department of Pediatrics, and., McGrath KE; Center for Pediatric Biomedical Research, Department of Pediatrics, and., Palis J; Center for Pediatric Biomedical Research, Department of Pediatrics, and. |
| المصدر: | Blood [Blood] 2014 Jul 10; Vol. 124 (2), pp. 277-86. Date of Electronic Publication: 2014 Apr 15. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | Cell Movement*/drug effects , Cell Movement*/genetics , Cell Movement*/radiation effects , Radiation Injuries, Experimental*/genetics , Radiation Injuries, Experimental*/pathology, Chemokine CXCL12/*physiology , Megakaryocytes/*cytology , Megakaryocytes/*physiology , Stem Cell Niche/*genetics , Thrombopoiesis/*genetics, Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/drug effects ; Bone Marrow Cells/physiology ; Bone Marrow Cells/radiation effects ; Cell Differentiation/drug effects ; Cell Differentiation/genetics ; Cell Differentiation/radiation effects ; Cells, Cultured ; Chemokine CXCL12/administration & dosage ; Female ; Megakaryocyte Progenitor Cells/cytology ; Megakaryocyte Progenitor Cells/drug effects ; Megakaryocyte Progenitor Cells/physiology ; Megakaryocyte Progenitor Cells/radiation effects ; Megakaryocytes/drug effects ; Megakaryocytes/radiation effects ; Mice ; Mice, Inbred C57BL ; Receptors, CXCR4/administration & dosage ; Receptors, CXCR4/metabolism ; Stem Cell Niche/drug effects ; Stem Cell Niche/radiation effects ; Thrombopoiesis/drug effects ; Thrombopoiesis/radiation effects |
| مستخلص: | Megakaryocyte (MK) development in the bone marrow progresses spatially from the endosteal niche, which promotes MK progenitor proliferation, to the sinusoidal vascular niche, the site of terminal maturation and thrombopoiesis. The chemokine stromal cell-derived factor-1 (SDF-1), signaling through CXCR4, is implicated in the maturational chemotaxis of MKs toward sinusoidal vessels. Here, we demonstrate that both IV administration of SDF-1 and stabilization of endogenous SDF-1 acutely increase MK-vasculature association and thrombopoiesis with no change in MK number. In the setting of radiation injury, we find dynamic fluctuations in marrow SDF-1 distribution that spatially and temporally correlate with variations in MK niche occupancy. Stabilization of altered SDF-1 gradients directly affects MK location. Importantly, these SDF-1-mediated changes have functional consequences for platelet production, as the movement of MKs away from the vasculature decreases circulating platelets, while MK association with the vasculature increases circulating platelets. Finally, we demonstrate that manipulation of SDF-1 gradients can improve radiation-induced thrombocytopenia in a manner additive with earlier TPO treatment. Taken together, our data support the concept that SDF-1 regulates the spatial distribution of MKs in the marrow and consequently circulating platelet numbers. This knowledge of the microenvironmental regulation of the MK lineage could lead to improved therapeutic strategies for thrombocytopenia. (© 2014 by The American Society of Hematology.) |
| التعليقات: | Comment in: Blood. 2014 Jul 10;124(2):161-3. (PMID: 25013161) |
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| معلومات مُعتمدة: | U19AI091036 United States AI NIAID NIH HHS; R01AI080401 United States AI NIAID NIH HHS; T32 GM007356 United States GM NIGMS NIH HHS; U01 AI107276 United States AI NIAID NIH HHS; F30DK100164 United States DK NIDDK NIH HHS; U19 AI091036 United States AI NIAID NIH HHS; R01 AI080401 United States AI NIAID NIH HHS; F30 DK100164 United States DK NIDDK NIH HHS; T32GM07356 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (Chemokine CXCL12) 0 (Cxcl12 protein, mouse) 0 (Receptors, CXCR4) |
| تواريخ الأحداث: | Date Created: 20140417 Date Completed: 20140925 Latest Revision: 20211021 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC4093683 |
| DOI: | 10.1182/blood-2014-01-547638 |
| PMID: | 24735964 |
| قاعدة البيانات: | MEDLINE |
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