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Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells
Author(s) -
Guidi Novella,
Sacma Mehmet,
Ständker Ludger,
Soller Karin,
Marka Gina,
Eiwen Karina,
Weiss Johannes M,
Kirchhoff Frank,
Weil Tanja,
Cancelas Jose A,
Florian Maria Carolina,
Geiger Hartmut
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201694969
Subject(s) - biology , osteopontin , phenotype , stem cell , haematopoiesis , microbiology and biotechnology , hematopoietic stem cell , genetics , cancer research , immunology , gene
Upon aging, hematopoietic stem cells ( HSC s) 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 HSC s 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 HSC s to thrombin‐cleaved OPN attenuates aging of old HSC s, 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.