Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells
| العنوان: | Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells |
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| المؤلفون: | Karin Soller, Tanja Weil, Jose A. Cancelas, Novella Guidi, Johannes M. Weiss, Ludger Ständker, Gina Marka, Frank Kirchhoff, Hartmut Geiger, Karina Eiwen, Maria Carolina Florian, Mehmet Sacma |
| المصدر: | The EMBO Journal EMBO Journal |
| بيانات النشر: | John Wiley and Sons Inc., 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Aging, Myeloid, osteopontin, Stem cells, localization, alpha(9)beta(1), Mice, 0302 clinical medicine, DDC 570 / Life sciences, Osteopontin, requirements, stromal cells, 0303 health sciences, General Neuroscience, Stem Cells, Hematopoietic stem cell, hemic and immune systems, progenitor cells, Articles, Corrigenda, Maus, Cell biology, Haematopoiesis, niche, Phenotype, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Stem cell, Stromal cell, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, stomatognathic system, ddc:570, component, medicine, Animals, Regeneration, Humans, Progenitor cell, Molecular Biology, 030304 developmental biology, Nische, bone-marrow niche, General Immunology and Microbiology, Altern, Hematopoietic Stem Cells, microenvironment, Mice, Inbred C57BL, Lokalisation, Ageing, 030104 developmental biology, biology.protein, Mesenchymal stem cells, hematopoietic stem cell, Bone marrow, Cell Adhesion, Polarity & Cytoskeleton, Hematopoietic stem cells |
| الوصف: | Upon aging, hematopoietic stem cells (HSCs) undergo changes in function and structure, including skewing to myeloid lineages, lower reconstitution potential and loss of protein polarity. While stem cell intrinsic mechanisms are known to contribute to HSC aging, little is known on whether age-related changes in the bone marrow niche regulate HSC aging. Upon aging, the expression of osteopontin (OPN) in the murine bone marrow stroma is reduced. Exposure of young HSCs to an OPN knockout niche results in a decrease in engraftment, an increase in long-term HSC frequency and loss of stem cell polarity. Exposure of aged HSCs to thrombin-cleaved OPN attenuates aging of old HSCs, resulting in increased engraftment, decreased HSC frequency, increased stem cell polarity and a restored balance of lymphoid and myeloid cells in peripheral blood. Thus, our data suggest a critical role for reduced stroma-derived OPN for HSC aging and identify thrombin-cleaved OPN as a novel niche informed therapeutic approach for ameliorating HSC phenotypes associated with aging. publishedVersion |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1460-2075 0261-4189 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::36c6b80412477038cc8e3c62bc7c543bTest http://europepmc.org/articles/PMC5376966Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....36c6b80412477038cc8e3c62bc7c543b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602075 02614189 |
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